JP2007518750A - Flavonoid complexes with cyclodextrins - Google Patents

Abstract

The present invention relates to a complex of a specific flavonoid derivative, a composition of formula I comprising the derivative, a corresponding method for the preparation of the flavonoid derivative or composition thereof, and in particular to care for and protect the general condition of the skin or hair Or related to its use to improve. In Formula (1), Z _{1 to} Z ₄ and Z _{6 to} Z ₁₀ each independently represent H, OH, CH ₃ COO, alkoxy, hydroxyalkoxy, mono- or oligoglycoside group, and the alkoxy and hydroxyalkoxy groups described above Can be branched and unbranched and can have 1 to 18 C atoms. In formula (II), Z ₅ is a mono- or oligoglycoside group to which at least one group selected from a specific benzo molecule is bound to this glycoside group, in each case via an —O— group. .

Description

  The present invention relates to a complex of a specific flavonoid derivative, a composition comprising the derivative, a corresponding preparation method of the flavonoid derivative or a composition comprising it, and in particular the care, protection or improvement of the general condition of the skin or hair Relating to its use for.

  International patent application WO 02/69926 describes compounds of the formula

(Where
Z _{1 to} Z ₄ and Z _{6 to} Z ₁₀ each independently represent H, OH, CH ₃ COO, alkoxy, hydroxyalkoxy, mono- or oligoglycoside group, and the alkoxy and hydroxyalkoxy groups are branched and unbranched. Well, it can have 1 to 18 C atoms,

Is

Represents
Z ₅ is a mono- or oligoglycoside group, which in each case via an —O— group,

(Where
X, X ₁ , X ₂ and X ₃ each independently represent OH, CH ₃ COO, an alkoxy group having 1 to 8 C atoms or a monoglycoside group,
n is 0, 1, 2 or 3;
m is 0 or 1,
k is 0, 1, 2, 3 or 4;
M is H, Na or K)
And at least one group selected from
One or more hydrogen atoms of the OH group of the glycoside group in the substituents Z _{1 to} Z ₁₀ may be each independently substituted with an acetyl or alkyl group, and the sulfates or phosphates are each independently And may be bonded to one or more hydroxyl groups of the above groups in the substituents Z _{1 to} Z ₁₀ )
Is described. These compounds are suitable for use in cosmetic and pharmaceutical compositions. In particular, WO 02/69926 describes the suitability of these compounds for use as UV filters and as active ingredients for protection against oxidative stress and prevention of skin aging. Furthermore, it is stated that these compounds exhibit anti-allergic, anti-inflammatory, anti-inflammatory and anti-hypersensitivity properties and can therefore be used in particular for the therapeutic or prophylactic treatment of skin allergies, inflammation and hypersensitivity is doing. Particularly preferred representative examples here are kaempferol 3- (6 ″ -galloylglucoside) and kaempferol 3- (6 ″ -p-coumaryl glucoside), also referred to as tiriloside.

  German Patent DE 195 54 905 A1 describes, for example, a process for the preparation of a plant extract containing tiliroside and the use of the plant extract in pharmaceuticals and foods.

  German Patent DE 199 22 287 A1 describes tiliroside as a starting flavonoid for the preparation of tiliroside esters whose acid units contain 3 to 30 C atoms. These esters are used in cosmetics. However, DE 199 22 287 A1 does not describe any composition containing tiliroside.

  The previous European patent application EP03001616.0 describes that these compounds are suitable for the treatment of eczema. This compound is particularly advantageous for the treatment of atopic eczema, especially chyle, neurodermatitis, prurigo and proliferative dermatitis. This compound can significantly reduce acute symptoms, reduce the frequency of occurrence of acute symptoms, and generally contribute to improving skin conditions.

  When these compounds are used, they can be more easily mixed into the composition, the composition exhibits better storage stability, or the compound has increased bioavailability A form is desired.

  Surprisingly, it has been found that by complexing these compounds with cyclodextrins, a product is obtained that satisfies the above requirements in an excellent manner.

  Therefore, the present invention firstly provides the following complex compound of formula I

(Where
Z _{1 to} Z ₄ and Z _{6 to} Z ₁₀ each independently represent H, OH, CH ₃ COO, alkoxy, hydroxyalkoxy, mono- or oligoglycoside group, and the alkoxy and hydroxyalkoxy groups are branched and unbranched. Well, it can have 1 to 18 C atoms,

Is

Represents
Z ₅ is a mono- or oligoglycoside group, which in each case via an —O— group,

(Where
X, X ₁ , X ₂ and X ₃ each independently represent OH, CH ₃ COO, an alkoxy group having 1 to 8 C atoms or a monoglycoside group,
n is 0, 1, 2 or 3;
m is 0 or 1,
k is 0, 1, 2, 3 or 4;
M is H, Na or K)
And at least one group selected from
CD represents a cyclodextrin molecule,
o represents the number 1,
p represents a numerical value in the range of 0.5 to 3,
One or more hydrogen atoms are each acetyl or C ₁ ~ ₂₄ independently of each other OH groups of the glycoside radicals in the substituent Z ₁ to Z ₁₀ - it may be substituted with an alkyl group, sulfate or phosphate Each salt, independently of one another, may be bound to one or more hydroxyl groups of the above groups in the substituents Z _{1 to} Z ₁₀ ).

The present application is secondly a composition comprising a suitable excipient, the composition comprising -0.005 to 99% by weight of the complex compound of formula I according to claim 1 or a composition thereof. Including,
-0.002 to 70% by weight of cyclodextrin, and-0.001 to 60% by weight of at least one compound of formula II or

(Where
Z _{1 to} Z ₄ and Z _{6 to} Z ₁₀ each independently represent H, OH, CH ₃ COO, alkoxy, hydroxyalkoxy, mono- or oligoglycoside group, and the alkoxy and hydroxyalkoxy groups are branched and unbranched. Can have 1 to 18 C atoms,

Is

Represents
Z ₅ is a mono- or oligoglycoside group, which in each case via an —O— group,

(In the formula, X, X ₁ , X ₂ and X ₃ each independently represent OH, CH ₃ COO, an alkoxy group having 1 to 8 C atoms or a monoglycoside group, and n is 0, 1, 2 or 3, m is 0 or 1, k is 0, 1, 2, 3 or 4, and M is H, Na or K). cage, one or more hydrogen atoms are each acetyl or C ₁ ~ ₂₄ independently of each other OH groups of the glycoside radicals in the substituent Z ₁ to Z ₁₀ - it may be substituted with an alkyl group, sulfate or Each of the hydrochlorides may be bonded to one or more hydroxyl groups of the above groups in the substituents Z _{1 to} Z ₁₀ independently of each other)
Or a composition characterized in that it comprises a salt and / or derivative thereof that is topically tolerated.

  The composition according to the invention is generally a composition that can be used topically, for example a cosmetic or dermatological preparation, or a composition that can be used as a pharmaceutical or food or food supplement. The composition comprises excipients suitable for cosmetic or dermatological or pharmaceutical or food purposes, and optionally further suitable ingredients depending on the desired property profile.

  Cyclodextrins are composed of 6, 7, 8 or more α-1,4-linked glucose units, and cyclohexaamylose (alpha or α-cyclodextrin) has a structure.

It is characterized by.

  Cycloheptaamylose (beta attached to this glycosidic group in each case via an -O- group, ie β is at least one group selected from β-cyclodextrin) is a structure

It is characterized by.

  Cyclooctaamylose (gamma or γ-cyclodextrin) has a structure

It is characterized by.

  Cycloene amylose (delta-or δ-cyclodextrin) has a structure

It is characterized by.

  Cyclodextrins may be in the non-derivatized form (R = H) or in the derivatized form, eg, alkoxylated, hydroxyalkylated or alkylated, particularly propoxylated or methylated, at the R position. May be.

  This bioflavonoid / cyclodextrin complex is well known in principle.

  -K. Miyake, H.M. Arima et al. (Pharm. Dev. Techn. 5 (3) 2000, 399-407 describe the 1: 1 complex of rutin with β-cyclodextrin and its solubility and release behavior. -Cyclodextrin complexes and 2-hydroxypropyl β-cyclodextrin complexes have been found to be particularly stable, according to this document, α- and γ-cyclodextrin complexes can be used to complex rutin. In general, it is less suitable than β-cyclodextrin complexes.

  TK Nguyen, H. Gallons, C. Chemtob, Congr. Int. Technol. Pharm., 6th (1992), Vol 5, 408-16408-416 similarly describe various cyclodextrin complexes of rutin. ing. Here, 2,6-di-O-methyl-β-cyclodextrin complexes have been shown to be particularly soluble and complexes with rutin: cyclodextrin molar ratios of 1: 1 and 1: 2 are described. ing.

  European patent application EP-A-796624 describes complexes of isoflavones with β- and γ-cyclodextrins in soybeans or fermented soybeans. Complexing increases the solubility of the isoflavone and reduces its bitterness.

  Complexes of rutin with -β- and γ-cyclodextrins and their use as antioxidants are described in Japanese patent application JP 05/9137499.

  -Drinks containing cyclodextrin complexes of quercetin glycosides are described in Japanese patent application JP07 / 0775536.

  -Japanese patent application JP 05/186344 describes a composition comprising vitamin C and a cyclodextrin complex of vitamin P that improves the bioabsorption of vitamin C. Rutin, hesperidin and eriocitrin complexes have been described, for example rutin / β-cyclodextrin complexes having a molar ratio of 1.2.

  -S. Dimova, R. Mugabowindekwe et al., Int. J. Pharm. 26381-2) 2003, pages 95-103, the effect of 3-methoxyquercetin complex with hydroxypropyl β-cyclodextrin on nasal epithelial cells It is being considered.

  -R. Ficarra, S. Tommasini et al .; J. Pharm. Biomed. Analysis 29 (6) 2002, 1005-1014, characterized by β-cyclodextrin complexes of various flavonoids (resperetin, hesperidin, naringenin, naringin) It is evaluated.

  -R.-L. Wang, Yu Yang et al .; Yinging Huaxue 19 (7) 2002, 702-704 is the stability and solubility of various β-cyclodextrin complexes of various flavonoids (rutin, quercetin, morin). Are comparing. Here it is shown that the methyl-β-cyclodextrin complex has a particularly high solubility.

  K. Hostettmann, M. Lederer and A. Marston; Phytochemical Analysis 1186) 2000, 380-382, examines the elution effect of 2-hydroxypropyl-β-cyclodextrin on flavonoids absorbed on cellulose. .

  In a manner unforeseen by those skilled in the art, it has been found that a composition for topical use comprising the complex compound of formula I or the compound of formula II and a cyclodextrin results in an improvement of the disadvantages of the prior art.

Here, cyclodextrin .gamma.-cyclodextrin to be used, preferably one or more hydroxyl groups is C ₁ ~ ₂₄ - alkyl or C ₁ ~ ₂₄ - .gamma.-cyclodextrin are substituted with hydroxyalkyl, such as, in particular, Particular preference is given to hydroxypropyl-γ-cyclodextrin or a mixture of cyclodextrins comprising at least 30% by weight of the above-mentioned γ-cyclodextrin, based on the total weight of the cyclodextrin mixture.

  The cyclodextrin content is 0.01 to 20.0% by weight, preferably 0.05 to 10.0% by weight, particularly preferably 0.1 to 5.0% by weight, based on the total weight of the composition. It is further advantageous that The proportion of the compound of formula II in the composition is preferably from 0.01 to 20% by weight, particularly preferably from 0.05 to 10% by weight, particularly preferably from 0.1 to 5% by weight, based on the total composition is there. The proportion of the compound of formula II in the composition is very preferably from 0.1 to 2% by weight, based on the total composition.

A combination of active ingredients according to the invention, or a cosmetic or dermatological composition comprising a combination of such active ingredients, is a satisfactory preparation in all respects. The person skilled in the art knows the composition according to the invention.
Providing a compound of formula I with enhanced bioavailability;
Maintain or restore the barrier properties of the skin well,
・ Counter to keep skin dry well,
• It was not foreseen to protect the skin better than the prior art compositions against environmental effects.

Surprisingly, the use of the complex compounds used in the present invention, or cosmetic or topical dermatological compositions having an active content of active ingredient combinations used according to the present invention,
-A state of sensitive or poor functioning skin with defects, or a state of sensitive or poor functioning with defects of skin appendages,
-Harmful changes in the environment (smoke, smog, reactive oxygen species, free radicals) and especially skin and skin appendages caused by light;
-Skin damage caused by light,
-Pruritus,
-Dry skin condition and stratum corneum barrier defects,
-Effective treatment and prevention of inflamed skin conditions and atopic eczema, seborrheic eczema, polymorphic photodermatoses, psoriasis, vitiligo. However, the complex compounds according to the invention, or cosmetic or topical dermatological compositions with an effective content of the complex compounds according to the invention, are surprisingly
-Soothing sensitive or irritated skin,
-Stimulation of intracellular DNA synthesis, particularly in deficient or low-function skin conditions;
-Protection of the skin itself and enhancement of repair mechanisms (eg for dysfunctional enzymes, DNA, lipids, proteins),
-Pre- and post-treatment in the case of topical use of laser and abrasive treatments, for example to help reduce wrinkles and scars, in order to deal with the resulting skin sensitivity and accelerate the process of regenerating damaged skin Also useful.

Therefore, according to the present invention,
Cosmetic or dermatological treatment or prevention of unwanted skin conditions,
Prevention and treatment of inflamed skin conditions (including atopic eczema),
・ Skin protection in the case of dry skin judged to be sensitive,
・ Protection of the skin against photoreaction,
Treatment and prevention of sensitive skin conditions,
The use of a composition comprising a complex compound of formula I or a compound of formula II and a cyclodextrin to enhance the desoxidative protection of the skin itself and / or to improve the protection of the skin against environmental effects is there.

  Compositions comprising the complex compounds or active ingredient combinations according to the invention have a synergistic effect on the individual components in all these uses.

  An advantage of the present invention is the use of cyclodextrins and / or cyclodextrin derivatives to increase the solubility of compounds of formula II. A further advantage is the use of cyclodextrins and / or cyclodextrin derivatives to improve the biological effect of the compounds of formula II.

In the flavonoid part of the compound of formula I or the compound of formula II, the alkoxy group is linear and has 1 to 12, preferably 1 to 8, C atoms. That is, these groups correspond to the formula —O— (CH ₂ ) _m —H, where m is 1, 2, 3, 4, 5, 6, 7 or 8, especially 1 to 5. To do.

In the flavonoid part of the compound of formula I or the compound of formula II, the hydroxyalkoxy group is straight-chain and has 2 to 12, preferably 2 to 8, C atoms. That is, these groups - in the formula -O- (CH _{2) n} -OH (wherein, n is 4, 5, 6, 7 or 8, in particular 2 to 5, specially preferably Is 2).

When one or more of the groups Z ₁ -Z ₄ and Z ₆ -Z ₁₀ of the flavonoid moiety of a compound of formula I or a compound of formula II refers to a mono- or oligoglycoside group, this glycoside group corresponds to the corresponding in formula I It is directly bonded to the benzene ring through an oxygen atom. The mono or oligoglycoside group is preferably composed of 1 to 3 glycoside units. These units are preferably selected from the group consisting of hexosyl groups, in particular rhamnosyl groups and glucosyl groups. However, other hexosyl groups such as allosyl, altrosyl, galactosyl, grosyl, idosyl, mannosyl and tarosyl can also be used advantageously. Pentosyl groups can also be used advantageously in the present invention.

The mono- or oligoglycoside group present in the group Z ₅ of the flavonoid moiety of the compound of the formula I or the compound of the formula II is bonded via an oxygen atom and is preferably composed of 1 to 3 glycoside units. . Preferred units in the groups Z _{1 to} Z ₄ and Z _{6 to} Z ₁₀ are also preferred for mono- or oligoglycoside groups present in the group Z ₅ . It is particularly preferred that the mono- or oligoglycoside group present in the group Z ₅ is selected from the group consisting of glucose, rhamnose and rutinose groups.

When X, X ₁ , X ₂ and / or X ₃ of the flavonoid moiety of the compound of formula I or the compound of formula II refer to a monoglycoside group, these glycoside groups are each connected to the corresponding benzene ring via an oxygen atom. Are connected. Preferred units in the groups Z _{1 to} Z ₄ and Z _{6 to} Z ₁₀ are also preferred for this monoglycoside group. A glucose group is particularly preferred when X, X ₁ , X ₂ and / or X ₃ refers to a monoglycoside group.

In a preferred embodiment of the present invention, in particular when increasing the water solubility of the flavonoid moiety of the compound of formula I or of the compound of formula II, polar groups are substituted, for example in each case independently of the sulfate or phosphate groups. It is bonded to one or more hydroxyl groups of the above groups in the groups Z _{1 to} Z ₁₀ . Suitable counterions are, for example, alkali metal or alkaline earth metal ions, which are selected, for example, from sodium or potassium.

In another preferred embodiment of the invention, the group having an aromatic moiety present in the substituent Z ₅ is bound to the mono- or oligoglycoside group also present in the group Z ₅ via the ester group —OOC—. Preferred are the flavonoid moieties of the formula I or II compounds.

  In another preferred embodiment of the invention, the sub-formula of formula I or formula II has the following groups: rutin, trishydroxyethylrutin (troxertin), isoquercetin, trishydroxyethylisoquercetin (troxeisoquercetin) And astragalin, and compounds from its sulfates and phosphates.

  In another preferred embodiment, the flavonoid moiety of the compound of formula I or the compound of formula II present in the composition of the invention is a compound of formula IIA,

(Where
R ¹ , R ² and R ³ each independently represent OH, CH ₃ COO, an alkoxy group having 1 to 8 C atoms or a monoglycoside group,
R ⁴ is a mono- or diglycoside group, which in each case through an —O— group,

(Wherein R ⁵ , R ⁶ and R ⁷ are each independently H or have the meaning of the radicals R ^{1 to} R ³ )
And at least one group selected from
Wherein the one or more hydrogen atoms are independently of each other OH group of the glycoside radical, acetyl or C ₁ ~ ₂₄ - it may be substituted with an alkyl group, independently of each other sulfate or phosphate, formula IIA Which may be bonded to one or more hydroxyl groups of
Selected from.

In a preferred embodiment, the group R ² of the compound of formula IIA is selected from OH, CH ₃ COO or an alkoxy group having 1 to 8 C atoms.

In compounds of formula IIA, all OH groups of the mono- or diglycoside group of R ⁴ are groups of the formula

It may be esterified with.

  However, it is preferred that only one or two of the groups derived from these groups are bound to a glycoside group.

When R ⁴ is a mono- or diglycoside group in which one or more hydrogen atoms of the OH group are substituted with acetyl or alkyl groups, all substitutable OH groups are substituted with acetyl or alkyl Is preferred.

  Of the alkoxy groups having 1 to 8 C atoms mentioned in the compound of formula IIA, a methoxy group is preferred. Of the alkyl groups having 1 to 8 C atoms mentioned in the compound of formula IIA, the methyl group is preferred.

  The mono and diglycoside groups mentioned in the compound of formula IIA are preferably composed of glucose units.

  Preferred compounds IIA1 to IIA13 selected from compounds of formula IIA are shown below.

  In the compounds of the above formulas IIA1 to IIA13, Me represents methyl and Ac represents acetyl.

  Of the compounds of formula IIA, particularly preferred are compounds of formula IIA1 and IIA2. Highly preferred is the compound of formula IIA1, ie tiliroside.

  In a further preferred embodiment, the flavonoid moiety of the compound of formula I or the compound of formula II present in the composition according to the invention is

But

Represents
Z _{1 to} Z ₄ and Z _{6 to} Z ₁₀ each independently represent H, OH, alkoxy, hydroxyalkoxy, mono- or oligoglycoside groups, the alkoxy and hydroxyalkoxy groups may be branched and unbranched, and 1 to Can have 18 C atoms,
Z ₅ , n, m, k and M have the meanings given in claim 1, but the groups X, X ₁ , X ₂ and X ₃ present in the substituent Z ₅ are each independently of each other OH, 1 Represents an alkoxy or monoglycoside group having ˜8 C atoms,
One or more hydrogen atoms are each independently of the other, C ₁ ~ ₂₄ of the OH groups of the glycoside radicals in the substituent Z ₁ to Z ₁₀ - alkyl group may be substituted by, sulfate or phosphate Are each independently selected from compounds that may be bonded to one or more hydroxyl groups of the above groups in the substituents Z _{1 to} Z ₁₀ .

In these flavonoid moieties of the compound of formula I or the compound of formula II, it is preferred that Z _{1 to} Z ₄ and Z _{6 to} Z ₁₀ each independently represent H, OH, alkoxy or hydroxyalkoxy.

In a further preferred embodiment, the compound of formula IIA present in the composition according to the invention is
R ¹ , R ² and R ³ each independently represent OH, an alkoxy group having 1 to 8 C atoms or a monoglycoside group,
R ⁴ is a mono- or diglycoside group, which in each case through an —O— group,

(Wherein R ⁵ , R ⁶ and R ⁷ each independently represent H, OH, an alkoxy group having 1 to 8 C atoms or a monoglycoside group)
And at least one group selected from
The one or more hydrogen atoms may each independently of the other OH group of the glycoside group, C ₁ ~ ₂₄ - may be substituted with an alkyl group, independently of each other sulfate or phosphate may also compounds of formula IIA Selected from compounds that may be bound to one or more hydroxyl groups.

In these compounds of formula IIA, it is preferred that R ^{1 to} R ³ each independently represent OH or an alkoxy group having 1 to 8 C atoms.

  Some flavonoid moieties of compounds of Formula I or Formula II, such as tiliroside, can be found in plants such as Altea, Aristolochia, Helianthemum, Lindera, Magnolia, Platanus. It can be isolated from plants of the genus (Platanus), Potentilla, Quercus, Rose, Sida, Sorbus and / or Tilia. These compounds can be further processed in isolated or non-isolated form. That is, for example, it can be mixed into the composition in the form of an extract, in the form of a purified extract, or in the form of a high-purity substance prepared from a plant extract. Of the above genera, the following species are preferred: That is, marshmallow (Althaea officinalis), hollyhock (Althaea rosea), Aristolochia heterophylla (Aristolochia heterophylla), Helianthum gromeratam (Lindelamegaphylla) , Platanus acerifolia, Platanus oxydentalis, Potentilla anserina, Quercus pusescens, Cork gassi uercus suber, Quercus laurifolia, Quercus ilex, Quercus imbriala, Quercus virginia, Quercus virialia, Quercus virilia Sida poeppigiana, Sida cordifolia, Sida glaziovi, Sorbus pendula, Tilia argenta and Tilia argentacodedata).

  When the composition according to the invention comprises tiliroside, in a further preferred embodiment the compound is in the form of a plant extract, a purified plant extract form or a highly pure substance prepared from a plant extract. Used for preparation.

  In this type of composition, the plant extract contains for example 1 to 100% by weight of tiliroside. In one embodiment, the plant extract preferably comprises 5 to 90% by weight of tiliroside. In another embodiment, the plant extract comprises 30-100% by weight, particularly preferably 60-100% by weight, particularly preferably 90-100% by weight of tiliroside.

  In a further preferred embodiment, the plant extract was extracted and isolated from fern gradiobi plants.

  In all uses of the present invention that use tiliroside, tiliroside was isolated from, for example, synthetically obtained substance forms, plant extracts, purified plant extracts or individual substance forms, or plant extracts. It can be used in the form of a highly pure substance. In a preferred embodiment, tiliroside is used in the form of a plant extract, a purified plant extract, or a high purity material prepared from a plant extract.

  The flavonoid moieties of compounds of Formula I or Formula II are well known to those skilled in the art and are described in the literature (eg, Houben-Weyl, Method der organics Chemie [Methods of Organic Chemistry], Georg-Thieme-Viege, Can be isolated or prepared in a standard manner such as Stuttgart).

  For example, tiliroside is present in plants and can be isolated by extraction. Plant extracts are prepared by conventional extraction methods from plants or plant parts. Suitable extraction methods include immersion, re-immersion, digestion, stirred immersion, fluidized bed extraction, ultrasonic extraction, countercurrent extraction, leaching, re-leaching, evacolation, diacolation or soxhlet extractor Or solid / liquid extraction by continuous reflux.

  The solvent used for extraction can be, for example, water or alcohol.

  How these extractions are carried out in detail can be attributed to the general knowledge of those skilled in the art, and the resulting crude extract can be purified by common conventional methods.

  One possible synthetic route for tiliroside is, for example, B. Vermes, H. Wagner, Stud. Org. Chem. (Amsterdam) (1982), Volume date 1981, 11 (flavonoids, bioflavonoids), 161-167. And B. Vermes, VM Chari, H. Wagner, Helv. Chim. Acta (1981), 64 (4), 1964-1967.

The synthesis of tililoside is shown in Scheme 1. 4 ', 7-dibenzyl kaempferol (1) [H. Wagner, H. Danninger, O. Seligmann, M. Nogradi, L. Farkas, N. Farnsworth, Chem. Ber. 103 (1978) 3768], Reaction with 2,3,4-tri-O-acetyl-6-O-chloroacetyl-β-D-glucopyranosyl bromide (2) in the presence of Ag ₂ CO ₃ and pyridine gives compound 3 . Compound 2 can be prepared by the method described in DY Gagnaire, P.J.A. Watero, Carbohydrate Res. 28 (1973) 1965. Careful acetylation following debenzylation of compound 3 using a catalyst gives compound 4 from which the chloroacetyl group is removed using thiourea to give compound 5. In this compound, only one hydroxyl group is free, meaning that the esterification of compound 5 can proceed selectively. Esterification of acid chloride with p-acetylcoumaroyl chloride 6 can be carried out in a mixture of pyridine and dichloromethane. To ensure complete esterification, an excess of acid chloride and a long reaction time at room temperature (about 96 hours) are required. The final step, selective saponification of the seven acetyl groups of compound 7, can be performed by the method described in G. Zemplen, Chem. Ber. 59 (1926) 1258. This is carried out using a catalytic amount of NaOCH ₃ and a calculated amount of methanol.

  Other flavonoid moieties of the compounds of formula I or II can be obtained by routine modification of the synthesis shown in Scheme 1. Depending on the target molecule, different starting materials are used here, ie optionally other protected flavonoids, sugar components and groups that may be linked to the sugar component.

  Esterification of a glycoside OH group using an aromatic sulfonic acid unit can be performed, for example, by the method described in AB Foster et al., J. Chem. Soc. (1954), pages 3625-3629. According to this method, the sugar component can be reacted with the corresponding aromatic sulfonyl chloride, for example in pyridine.

Etherification of a glycoside OH group using an aromatic group can be performed, for example, by the method described in P. Beraud et al., Tetrahedron Let. 30 (3) (1989), pages 325-326. In this Mitsunobu reaction, etherification is performed, for example, by dissolving a sugar component in pyridine together with triphenylphosphine PPh ₃ and reacting the solution with the corresponding phenol component and diethyl azodicarboxylate.

  Etherification of a glycoside OH group using a saturated hydrocarbon group can be performed, for example, by the method described in M. Goebel et al., Tetrahedron 53 (9) (1997) 3123-3134. Etherification is carried out in dry dimethylformamide under inert gas atmosphere by carefully adding sodium hydride to the sugar component and then carefully reacting the mixture with a suitable alkylating agent such as the corresponding bromide.

  Complex compounds of formula I can be prepared by reacting a compound of formula II with cyclodextrin in solution, preferably at elevated temperature. The invention further relates to a corresponding process.

  It has been found that complexes containing about 2 moles of cyclodextrin per mole of flavonoid of formula II particularly satisfy the requirements of the present invention. Thus, according to the present invention, it is preferred that o in Formula I is 1 and p is in the range of 1.75 to 2.1, preferably p is 2.

  If cyclodextrin is used in excess or precisely in a 2: 1 molar ratio to the flavonoid, the corresponding compound can be prepared.

  In a preferred embodiment of the invention, the composition comprises a body against oxidative stress, characterized in that it comprises one or more further antioxidants in addition to one or more compounds of the formula I or formula II A composition for protecting cells, particularly for reducing skin aging.

There are many identified substances well known in the expert literature that can be used as antioxidants. They include, for example, peptides such as amino acids (eg glycine, histidine, tyrosine, tryptophan) and derivatives thereof, imidazoles (eg urocanic acid) and derivatives thereof, D, L-carnosine, D-carnosine, L-carnosine and derivatives thereof (eg Anserine), carotenoids, carotenes (eg α-carotene, β-carotene, lycopene) and derivatives thereof, chlorogenic acid and derivatives thereof, lipoic acid and derivatives thereof (eg dihydrolipoic acid), aurothioglucose, propylthiouracil and other thiols (E.g. thioredoxin, glutathione, cysteine, cystine, cystamine and its glycosyl, N-acetyl, methyl, ethyl, propyl, amyl, butyl and lauryl, palmitoyl, oleyl, γ- Linoleyl, cholesteryl and glyceryl esters) and their salts, dilauryl thiodipropionate, distearyl thiodipropionate, thiodipropionic acid and its derivatives (esters, ethers, peptides, lipids, nucleotides, nucleosides and salts) and very Low tolerated doses (eg pmol to μmol / kg) of sulfoximine compounds (eg butionine sulfoximine, homocysteine sulfoximine, butionine sulfone, penta-, hexa- and heptathionin sulfoximine); In addition, (metal) chelating agents (for example, α-hydroxy fatty acid, palmitic acid, phytic acid, lactoferrin), α-hydroxy acid (for example, citric acid, lactic acid, malic acid), humic acid, bile acid, bile extract, bilirubin, bile Chlorophyll, EDTA EGTA and derivatives thereof, unsaturated fatty acids and derivatives thereof, vitamin C and derivatives (eg ascorbyl palmitate, magnesium ascorbyl phosphate, ascorbyl acetate), tocopherols and derivatives (eg vitamin E acetate), vitamin A and derivatives (eg vitamin A palmitate) ), And coniferyl benzoate, rutinic acid and its derivatives, α-glycosyl rutin, ferulic acid, furfurylidene glucitol, carnosine, butylhydroxytoluene, butylhydroxyanisole, nordihydroguaiaretic acid, trihydroxybutyrophenone , Quercetin, uric acid and its derivatives, mannose and its derivatives, zinc and its derivatives (eg ZnO, ZnSO ₄ ), selenium and There are derivatives thereof (e.g. selenomethionin), stilbene and derivatives thereof (e.g. stilbene oxide, trans-stilbene oxide).

  Mixtures of antioxidants are likewise suitable for use in the cosmetic composition according to the invention. Known and commercially available mixtures include, for example, as active ingredients lecithin, L-(+)-ascorbyl palmitate and citric acid (eg (eg Oxynex® AP), natural tocopherol, L-(+)- Ascorbyl palmitate, L-(+)-ascorbic acid and citric acid (eg Oxynex® K LIQUID), naturally derived tocopherol extract, L-(+)-ascorbyl palmitate, L-(+)-ascorbine Acids and citric acids (eg Oxynex® L LIQUID), DL-α-tocopherol, L-(+)-ascorbyl palmitate, citric acid and lecithin (eg Oxynex® LM) or butylhydroxytoluene (BHT), L-(+)-ascorbyl palmitate and citric acid (eg Oxy ex.RTM. 2004) This type of antioxidant is usually in a ratio of 1000: 1 to 1: 1000 with the compound of formula I or II in such a composition, preferably Used in an amount of 100: 1 to 1: 100.

The composition according to the invention can contain vitamins as a further component. The cosmetic composition according to the present invention comprises vitamin A, vitamin A propionate, vitamin A palmitate, vitamin A acetate, retinol, vitamin B, thiamine chloride hydrochloride (vitamin B ₁ ), riboflavin (vitamin B ₂ ), nicotinamide, vitamin C (Ascorbic acid), vitamin D, ergocalciferol (vitamin D ₂ ), vitamin E, DL-α-tocopherol, tocopherol E acetate, tocopherol hydrogen succinate, vitamin K ₁ , esculin (vitamin P active ingredient), thiamine ( vitamin B _1), nicotinic acid (niacin), pyridoxine, pyridoxal, pyridoxamine (vitamin B _6), pantothenic acid, biotin, may contain vitamins and vitamin derivatives selected from folic acid and cobalamine (vitamin B ₁₂₎ preferably Vitamin A palmitate, vitamin C and derivatives thereof, DL-alpha-tocopherol, tocopherol E acetate, nicotinic acid, it is particularly preferred to include a pantothenic acid and biotin. Vitamins are usually used with compounds of formula I or formula II in a ratio ranging from 1000: 1 to 1: 1000, preferably in an amount of 100: 1 to 1: 100.

  Of the phenols with antioxidant activity, polyphenols, some of which are naturally derived, are of particular interest for applications in the pharmaceutical, cosmetic or nutrition field. For example, flavonoids or bioflavonoids, mainly known as plant dyes, often have potential as antioxidants. K. Lemanska, H. Szymusiak, B. Tyrakowski, R. Zielinski, I.M.C.M.Rietjens; Current Topics in Biophysics 2000, 24 (2), pages 101-108 are mono and dihydroxyflavones It is about the effect of. Therein, dihydroxyflavones containing an OH group adjacent to the keto functional group or an OH group in the 3 ′, 4′- or 6,7- or 7,8-position have antioxidant properties, It has been identified that other mono and dihydroxy flavones may not have antioxidant properties.

  Quercetin (cyanidanol, cyanidenolon 1522, meletin, sophoretin, erythine, 3,3 ', 4', 5,7-pentahydroxyflavone) is often cited as a particularly effective antioxidant (eg C A. Rice-Evans, N. J. Miller, G. Pageanga, Trends in Plant Science 1997, 2 (4), pages 152-159). K. Lemanska, H. Szymusiak, B. Tyrakowski, R. Zielinski, A.E.M.F.Soffers, I.M.M.M.Rietjens; Free Radical Biology & Medicine 2001, 31-88 (1980) Page examines the pH dependence of the antioxidant action of hydroxyflavones. Quercetin exhibits the greatest activity among the structures studied over a wide range of pH.

  Furthermore, suitable antioxidants are compounds of the formula III described in the earlier German patent application DE 102444282.7.

(Wherein R ^{1 to} R ¹⁰ may be the same or different,
-H
− OR ¹¹
A linear or branched C ₁ -to C ₂₀ -alkyl group,
- linear or branched C ₃ - from C ₂₀ - alkenyl group,
A linear or branched C ₁ -to C ₂₀ -hydroxyalkyl group (the hydroxyl group may be bound to the primary or secondary carbon atom of the chain, and the alkyl chain may be intervened by oxygen) And / or —C ₃ — to C ₁₀ -cycloalkyl group and / or C ₃ — to C ₁₂ -cycloalkenyl group (the ring may be bridged by a — (CH ₂ ) _n — group, n = 1 to 3),
Selected from
-All OR ¹¹ are independent of each other,
-OH
A linear or branched C ₁ -to C ₂₀ -alkoxy group,
- linear or branched C ₃ - from C ₂₀ - alkenyloxy group,
A straight-chain or branched C ₁ -to C ₂₀ -hydroxyalkoxy group (the hydroxyl group may be bound to the first or second carbon atom of the chain, and the alkyl chain may be intervened by oxygen) And / or —C ₃ — to C ₁₀ -cycloalkoxy group and / or C ₃ — to C ₁₂ -cycloalkenyloxy group (the ring may be bridged by a — (CH ₂ ) _n — group, n = 1 to 3), and / or -mono and / or oligoglycosyl groups
However,
At least four groups of R ^{1 to} R ⁷ represent OH, and there are at least two adjacent pairs of —OH groups in the molecule,
-Or R ² , R ⁵ and R ⁶ represent OH and the groups R ¹ , R ³ , R ⁴ and R ⁷ to ¹⁰ represent H)
Particularly preferred compositions according to the invention comprise UV filters in addition to the compounds of formula I or formula II.

  The use of dibenzoylmethane derivatives, which are particularly preferred as UV-A filters, together with compounds of the formula I or II provide further advantages. That is, the presence of the compound of formula I or formula II further stabilizes the UV-sensitive dibenzoylmethane derivative. Accordingly, the present invention further relates to the use of a compound of formula I or formula II for the stabilization of dibenzoylmethane derivatives in a composition.

Basically, all UV filters are suitable for combination with the compounds of formula I or formula II of the present invention. Particularly preferred are UV filters whose physiological receptivity has already been demonstrated. There are many identified materials well known in the expert literature for both UVA and UVB filters. For example,
Benzylidene camphor derivatives, such as 3- (4′-methylbenzylidene) -dl-camphor (eg Eusolex® 6300), 3-benzylidene camphor (eg Mexoryl® SD), N-{(2 and 4) -[(2-oxoborn-3-ylidene) methyl] benzyl} acrylamide (eg Mexoryl® SW), N, N, N-trimethyl 4- (2-oxoborn-3-ylidenemethyl) anilinium methyl sulfate (eg Polymers of (Mexoryl® SK) or (2-oxoborn-3-ylidene) toluene-4-sulfonic acid (eg Mexoryl® SL),
Benzoylmethane or dibenzoylmethane, such as 1- (4-tert-butylphenyl) -3- (4-methoxyphenyl) propane-1,3-dione (eg Eusolex® 9020) or 4-isopropyldibenzoylmethane (For example, Eusolex® 8020),
Benzophenone, such as 2-hydroxy-4-methoxybenzophenone (eg Eusolex® 4360) or 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid and its sodium salt (eg Uvinul® MS-40),
Methoxycinnamate esters such as octyl methoxycinnamate (eg Eusolex® 2292), isopentyl 4-methoxycinnamate, eg a mixture of its isomers (eg Neo Heliopan® E1000),
Salicylate derivatives such as 2-ethylhexyl salicylate (eg Eusolex® OS), 4-isopropylbenzyl salicylate (eg Megasol®) or 3,3,5-trimethylcyclohexyl salicylate (eg Eusolex® HMS) ,
4-aminobenzoic acid and derivatives such as 4-aminobenzoic acid, 2-ethylhexyl 4- (dimethylamino) benzoate (eg Eusolex® 6007), ethoxylated ethyl 4-aminobenzoate (eg Uvinul® P25) ),
Phenylbenzimidazole sulfonic acid, such as 2-phenylbenzimidazole-5-sulfonic acid and its potassium, sodium and triethanolamine salts (eg Eusolex® 232), 2,2- (1,4-phenylene) bisbenz Imidazole-4,6-disulfonic acid and its salts (eg Neoheliopan® AP) or 2,2- (1,4-phenylene) bisbenzimidazole-6-sulfonic acid;
In still other substances, for example,
2-ethylhexyl 2-cyano-3,3-diphenyl acrylate (eg Eusolex® OCR),
-3,3 ′-(1,4-phenylenedimethylene) bis (7,7-dimethyl-2-oxobicyclo [2.2.1] hept-1-ylmethanesulfonic acid and its salts (eg, Mexoryl® SX) and -2,4,6-trianilino- (p-carbo-2'-ethylhexyl-1'-oxy) -1,3,5-triazine (e.g. Uvinul <(R)> T150)
-Hexyl 2- (4-diethylamino-2-hydroxybenzoyl) benzoate (eg Uvinul® UVA Plus, BASF).

  The compounds listed are to be considered as examples only. It is of course possible to use other UV filters.

  These organic UV filters are generally incorporated into cosmetic preparations in an amount of 0.5 to 10% by weight, preferably 1 to 8% by weight.

Other suitable organic UV filters are, for example,
-2- (2H-benzotriazol-2-yl) -4-methyl-6- (2-methyl-3- (1,3,3,3-tetramethyl-1- (trimethylsilyloxy) disiloxanyl) propyl) Phenol (e.g. Silatizole (R)),
-2-ethylhexyl 4,4 ′-[(6- [4-((1,1-dimethylethyl) aminocarbonyl) phenylamino] -1,3,5-triazine-2,4-diyl) diimino] bis ( Benzoate) (eg Uvasorb® HEB),
-[Alpha]-(trimethylsilyl)-[omega]-[trimethylsilyl) oxy] poly [oxy (dimethyl [and about 6% methyl [2- [p- [2,2-bis (ethoxycarbonyl] vinyl] phenoxy] -1-methylene Ethyl], about 1.5% methyl [3- [p- [2,2-bis (ethoxycarbonyl) vinyl]) phenoxy) propenyl) and 0.1-0.4% (methylhydrogen] silylene]] (N≈60) (CAS No. 2057474-1)
-2,2′-methylenebis (6- (2H-benzotriazol-2-yl) -4- (1,1,3,3-tetramethylbutyl) phenol) (CAS No. 103597-45-1)
-2,2 '-(1,4-phenylene) bis (1H-benzimidazole-4,6-disulfonic acid, monosodium salt) (CAS No. 180898-37-7) and -2,4-bis {[ 4- (2-ethylhexyloxy) -2-hydroxy] phenyl} -6- (4-methoxyphenyl) -1,3,5-triazine (CAS No. 103597-45, 187393-00-6),
-2-ethylhexyl 4,4 ′-[(6- [4-((1,1-dimethylethyl) aminocarbonyl) phenylamino] -1,3,5-triazine-2,4-diyl) diimino] bis ( Benzoate) (e.g. Uvasorb (R) HEB).

  Another suitable UV filter is also a methoxyflavone corresponding to the previous German patent application DE 10232595.2.

  Organic UV filters are generally incorporated into cosmetic formulations in an amount of 0.5 to 20% by weight, preferably 1 to 15% by weight.

  Possible inorganic UV filters are, for example, a group of titanium dioxide such as coated titanium dioxide (eg Eusolex® T-2000, Eusolex® T-AQUA, Eusolex® T-AVO), zinc There are those from the group of oxides (eg Sachtotec®), the group of iron oxides, and also the group of cerium oxides. These inorganic UV filters are generally incorporated into cosmetic preparations in an amount of 0.5 to 20% by weight, preferably 2 to 10% by weight.

  Preferred compounds with UV-filtering properties are 3- (4′-methylbenzylidene) -dl-camphor, 1- (4-tert-butylphenyl) -3- (4-methoxyphenyl) propane-1,3-dione 4-isopropyldibenzoylmethane, 2-hydroxy-4-methoxybenzophenone, octylmethoxycinnamate, 3,3,5-trimethylcyclohexyl salicylate, 2-ethylhexyl 4- (dimethylamino) benzoate, 2-ethylhexyl 2-cyano- 3,3-diphenyl acrylate, 2-phenylbenzimidazole-5-sulfonic acid and its potassium, sodium and triethanolamine salts.

  By combining one or more compounds of formula I or formula II with another UV filter, the protective action against the harmful effects of UV irradiation can be optimized.

  Optimized compositions include, for example, organic UV filters 4'-methoxy-6-hydroxyflavone and 1- (4-tert-butylphenyl) -3- (4-methoxyphenyl) propane-1,3-dione And combinations with 3- (4′-methylbenzylidene) -dl-camphor. This combination provides a wide range of protection and can be compensated for by adding inorganic UV filters such as titanium dioxide particulates.

All the UV filters can also be used in encapsulated form. In particular, the organic UV filter is advantageously used in encapsulated form. Specifically, the following advantages are brought about:
-The hydrophilicity of the capsule wall can be set independently of the solubility of the UV filter. Thus, for example, it is possible to mix a hydrophobic UV filter into a purely aqueous composition. Furthermore, an oil-like impression upon application of a composition comprising a hydrophobic UV filter, which is often considered unpleasant, is suppressed.

  Certain UV filters, in particular dibenzoylmethane derivatives, only slightly reduce the light stability in cosmetic compositions. Encapsulation of these filters, or compounds that impair the light stability of these filters, such as cinnamic acid derivatives, makes it possible to increase the light stability of the entire composition.

  -Skin penetration by organic UV filters and the possibility of associated hypersensitivity upon direct application to human skin has been repeatedly discussed in the literature. The proposed encapsulation of the corresponding substance suppresses this effect.

  -In general, the encapsulation of individual UV filters or other components may cause problems with the composition caused by interactions between the components of the individual composition, such as crystallization processes, precipitation and aggregate formation. Since the action is suppressed, it can be avoided.

  Therefore, according to the present invention, it is preferable to encapsulate one or more of the UV filters. The capsule is advantageously so small that it cannot be seen with the naked eye. In order to achieve the above effect, it is further necessary to make the capsule sufficiently stable so that little or no encapsulated active ingredient (UV filter) is released into the environment.

  Suitable capsules can have inorganic or organic polymer walls. For example, US Pat. No. 6,242,099B1 describes making suitable capsules with walls made of chitin, chitin derivatives or polyhydroxylated polyamines. Capsules that can be used particularly preferably in the present invention have walls obtained by sol-gels as described in the patent applications WO00 / 09652, WO00 / 72806 and WO00 / 71084. Here too, capsules whose walls are composed of silica gel (silica; undefined silicon oxide / silicon hydroxide) are preferred. The production of the corresponding capsules is well known to the person skilled in the art, for example from the cited patent application, the content of which is also clearly belonging to the subject of this application.

  The capsules in the composition according to the invention are preferably present in an amount that ensures that the encapsulated UV filter is present in the composition in the amounts described above.

  The composition according to the invention may further comprise other conventional skin protecting or skin care active ingredients. These can in principle be any active ingredient known to the person skilled in the art.

  These may be chromone derivatives. As used herein, the term chromone derivative preferably refers to a specific chromen-2-one derivative that is suitable as an active ingredient for the prophylactic treatment of human skin and human hair against the aging process and harmful environmental effects. Means. At the same time they are unlikely to irritate the skin and have a positive effect on the water binding in the skin, maintaining or increasing the elasticity of the skin and thus promoting the smoothness of the skin . These compounds are preferably of formula IV.

(Where
R ¹ and R ² may be the same or different,
- H, -C (= O) -R 7, -C (= O) -OR 7,
A linear or branched C ₁ -to C ₂₀ -alkyl group,
A straight-chain or branched C ₃ -to C ₂₀ -alkenyl group, a straight-chain or branched C ₁ -to C ₂₀ -hydroxyalkyl group (the hydroxyl group is bonded to the first or second carbon atom of the chain) In addition, the alkyl chain may also be mediated by oxygen) and / or —C ₃ — to C ₁₀ -cycloalkyl groups and / or C ₃ — to C ₁₂ -cycloalkenyl groups (the ring is — (CH ₂ ) may be bridged by an _n -group, n = 1-3)
Selected from
R ³ represents H or a linear or branched C ₁ -to C ₂₀ -alkyl group;
R ⁴ represents H or OR ⁸ ,
R ⁵ and R ⁶ may be the same or different,
--H, -OH,
A linear or branched C ₁ -to C ₂₀ -alkyl group,
- linear or branched C ₃ - from C ₂₀ - alkenyl group,
A linear or branched C ₁ -to C ₂₀ -hydroxyalkyl group (the hydroxyl group may be bound to the primary or secondary carbon atom of the chain, and the alkyl chain may be intervened by oxygen)
Selected from
R ⁷ represents H, a linear or branched C ₁ -to C ₂₀ -alkyl group, a polyhydroxyl compound, such as an ascorbic acid group or a glucoside group, preferably
R ⁸ represents H or a linear or branched C ₁ -to C ₂₀ -alkyl group,
At least two of the substituents R ¹ , R ² , R ^{4 to} R ⁶ are not H, or at least one substituent of R ¹ and R ² is —C (═O) —R ⁷ or —C (═ O) —OR ⁷ is represented. )
The proportion of the compound or compounds selected for the chromone derivative in the composition according to the invention is preferably 0.001 to 5% by weight, particularly preferably 0.01 to 2% by weight, based on the total composition. is there.

  More preferably, the composition according to the invention comprises at least one repellent. The repellent is preferably N, N-diethyl-3-methylbenzamide, ethyl 3- (acetylbutylamino) propionate, dimethyl phthalate, butopyronoxyl, 2,3,4,5-bis (2-butylene) tetrahydro-2 -Furaldehyde, N, N-diethylcaprylamide, N, N-diethylbenzamide, o-chloro-N, N-diethylbenzamide, dimethylcarbate, di-n-propylisocincomeronate, 2-ethylhexane-1 , 3-diol, N-octylbicycloheptene dicarboximide, piperonyl butoxide, 1- (2-methylpropoxycarbonyl) -2- (hydroxyethyl) piperidine or mixtures thereof. It is particularly preferred that it is selected from N, N-diethyl-3-methylbenzamide, ethyl 3- (acetylbutylamino) propionate 1- (2-methylpropoxycarbonyl) -2- (hydroxyethyl) piperidine or mixtures thereof.

  The composition according to the invention comprising a repellent is preferably an insect repellent. Insect repellents can be used in the form of solutions, gels, sticks, rollers, pump sprays and aerosol sprays, with solutions and sprays making up the majority of commercial products. The bases of these two product forms are usually formed by alcoholic solutions or aqueous / alcoholic solutions with the addition of fatting substances and some fragrance.

  Particularly preferred active ingredients are pyrimidinecarboxylic acids and / or aryl oximes.

  Pyrimidinecarboxylic acids are produced in halophilic microorganisms and play a role in regulating the permeability of these organisms (EA Galinski et al., Eur. J. Biochem., 149 (1985) 135-139. ). Among the pyrimidinecarboxylic acids that must be mentioned in particular are ectoine ((S) -1,4,5,6-tetrahydro-2-methyl-4-pyrimidinecarboxylic acid) and hydroxyectoine ((S, S) -1 2,4,5,6-Tetrahydro-5-hydroxy-2-methyl-4-pyrimidinecarboxylic acid and its derivatives, which stabilize enzymes and other biomolecules in aqueous solutions and organic solvents. These stabilize the enzyme especially against denaturing states such as salts, extreme pH values, surfactants, urea, guanidinium chloride and other compounds.

  Ectoine and ectoine derivatives such as hydroxyectoine can be used advantageously in pharmaceuticals. In particular, hydroxyectoine can be used in the preparation of a medicament for the treatment of skin diseases. Other areas of application of hydroxyectoin and other ectoine derivatives are areas where, for example, trehalose is used as an additive. Accordingly, ectoine derivatives such as hydroxyectoine can be used as a protective agent for dry yeast and bacterial cells. Pharmaceutical agents such as unglycosylated pharmaceutically active peptides and proteins, such as t-PA, can also be protected with ectoine or its derivatives.

  Among cosmetic applications, mention must be made of the use of ectoine and ectoin derivatives to care for aging, dry or irritated skin. That is, European patent application EP-A-0671161 especially applies ectoine and hydroxyectoine to cosmetic compositions such as powders, soaps, surfactant-containing cleansing products, lipsticks, rouges, makeup, care creams and sunscreens. The use is described.

  Here, the use of pyrimidinecarboxylic acids of the following formula V is preferred.

(Where
R ¹ is a radical H or C1~8- alkyl, R ² is a group H or C ₁ ~ ₄ - ^{alkyl, R 3, R 4, R} 5 and R ⁶ groups each, independently of one another H, OH, NH ₂ and C ₁ ~ ₄ - is a radical from alkyl). Preference is given to using pyrimidinecarboxylic acids in which R ² is a methyl or ethyl group and R ¹ or R ⁵ and R ⁶ are H. Pyrimidinecarboxylic acid ectoine ((S) -1,4,5,6-tetrahydro-2-methyl-4-pyrimidinecarboxylic acid) and hydroxyectoine ((S, S) -1,4,5,6-tetrahydro- The use of 5-hydroxy-2-methyl-4-pyrimidinecarboxylic acid) is particularly preferred. The composition according to the invention preferably comprises this type of pyrimidinecarboxylic acid in an amount of up to 15% by weight. Pyrimidinecarboxylic acids are preferably used in a ratio of 100: 1 to 1: 100 with respect to the compounds of formula I, particularly preferably in the range of 1:10 to 10: 1.

  Of the aryl oximes, the use of 2-hydroxy-5-methyllaurophenone oxime, also known as HMLO, LPO or F5, is preferred. Its suitability for use in cosmetic compositions is described, for example, in DE-A-4116123. Therefore, a composition comprising 2-hydroxy-5-methyllaurophenone oxime is suitable for the treatment of skin diseases accompanied by inflammation. This type of composition is used, for example, for the treatment of psoriasis, various forms of eczema, irritant and toxic dermatitis, UV dermatitis and other allergic and / or inflammatory diseases of the skin and skin appendages It is known that it can be. In addition to the compounds of formula I, the compositions according to the invention further comprising an aryl oxime, preferably 2-hydroxy-5-methyllaurophenone oxime, show surprising suitability for anti-inflammatory properties. The composition preferably comprises 0.01 to 10% by weight of aryl oxime, and the composition particularly preferably comprises 0.05 to 5% by weight of aryl oxime.

  Furthermore, as with the preferred embodiment of the invention, the composition according to the invention comprises at least one self-tanning.

  The advantageous self-tanning that can be used is, among others:

  5-Hydroxy-1,4-naphthoquinone (Yuglon) extracted from fresh walnut shell

And 2-hydroxy-1,4-naphthoquinone (lauson) produced in the leaves of henna

You must also list.

  1,3-dihydroxyacetone (DHA), which is a trifunctional sugar produced in the human body, and its derivatives are highly preferred.

Furthermore, the composition according to the invention can also comprise dyes and colored pigments. The dyes and color pigments can be selected from the corresponding positive list of the German Cosmetics Regulation or the EC list of cosmetic colorants. In most cases, these are the same dyes approved for food use. Advantageous colored pigments are, for example, titanium dioxide, mica, iron oxide (eg Fe ₂ O ₃ , Fe ₃ O ₄ , FeO (OH)) and / or tin oxide. Advantageous dyes are, for example, carmine, Berlin blue, chromium oxide green, ultramarine blue and / or manganese violet. It is particularly advantageous to select from the following list of dyes and / or colored pigments. The color index number (CIN) is from Rowe Color Index, 3rd Edition, Society of Dyers and Colorists, Bradford, England, 1971.

In addition, one or more substances can be conveniently selected from the following groups as dyes:
2,4-dihydroxyazobenzene, 1- (2′-chloro-4′-nitro-1′phenylazo) -2-hydroxynaphthalene, selesed, 2- (4-sulfo-1-naphthylazo) -1-naphthol-4 -Sulfonic acid, calcium salt of 2-hydroxy-1,2'-azonaphthalene-1'-sulfonic acid, calcium and barium of 1- (2-sulfo-4-methyl-1-phenylazo) -2-naphthylcarboxylic acid Salt, 1- (2-sulfo-1-naphthylazo) -2-hydroxynaphthalene-3-carboxylic acid calcium salt, 1- (4-sulfo-1-phenylazo) -2-naphthol-6-sulfonic acid aluminum salt 1- (4-sulfo-1-naphthylazo) -2-naphthol-3,6-disulfonic acid aluminum salt, 1- (4-sulfo-1-naphthylazo) -2-naphtho -6,8-disulfonic acid, aluminum salt of 4- (4-sulfo-1-phenylazo) -2- (4-sulfophenyl) -5-hydroxypyrazolone-3-carboxylic acid, of 4,5-dibromofluorescein Aluminum and zirconium salts Aluminum and zirconium salts of 2,4,5,7-tetrabromofluorescein, 3 ′, 4 ′, 5 ′, 6′-tetrachloro-2,4,5,7-tetrabromofluorescein and its Aluminum salt, aluminum salt of 2,4,5,7-tetraiodofluorescein, aluminum salt of quinophthalone disulfonic acid, aluminum salt of indigodisulfonic acid, red and black iron oxide (CIN: 77491 (red) and 77499 (black)) Iron oxide hydrate (CIN: 77492), ammonium manganese phosphate and titanium dioxide.

  Also advantageous are oil-soluble natural dyes such as, for example, paprika extract, β-carotene or cochineal.

Gel creams containing pearlescent pigments are also advantageous for the purposes of the present invention. The following types of nacreous pigments are particularly preferred:
1. Natural pearlescent pigments, for example
1. 1. “Pearl Essence” (Guanine / Hypoxanthine mixed crystals from fish scales) and `` Pearl layer '' (ground mussel shell)
2. 2. Single crystal pearlescent pigments such as bismuth oxychloride (BiOCl) Layered substrate pigments: for example mica / metal oxides Bases for pearlescent pigments are for example powdered pigments or bismuth oxychloride and / or titanium dioxide and castor oil dispersion of bismuth oxychloride and / or titanium dioxide on mica Form with liquid. For example, the glossy pigments mentioned in CIN 77163 are particularly advantageous.

  For example, the following pearlescent pigment types based on mica / metal oxide are also advantageous:

  For example, pearlescent pigments commercially available from Merck under the trade names Timiron, Colorona or Dichrona are particularly preferred.

The list of pearlescent pigments is of course not intended to be limiting. Pearlescent pigments that are advantageous for the purposes of the present invention are themselves obtainable from a number of routes. For example, another substrate other than mica can be coated with another metal oxide, such as silica. For example, TiO ₂ -and Fe ₂ O ₃ -coated SiO ₂ particles ("Ronasphere" grade), which are commercially available from Merck and are particularly suitable for optical reduction of fine wrinkles, are advantageous.

It is further advantageous to completely remove a substrate such as mica. Particular preference is given to pearlescent pigments prepared using SiO ₂ . Such pigments, which also have a goniochromatic effect, are commercially available, for example, from BASF under the trade name of Scopearl Fantastico.

  It is also advantageous to use Engelhard / Mearl pigments based on calcium sodium borosilicate coated with titanium dioxide. These are commercially available under the trade name Reflexs. Since the particle diameter is 40 to 80 μm, these also have the effect of being brilliant in addition to the color.

  Also particularly advantageous are effect pigments commercially available in various colors (yellow, red, green, blue) under the trade name Metasomes Standard / Glitter from Flora Tech. The sparkling particles are in the form of a mixture with various adjuvants and dyes (eg, dyes with color index (CI) numbers 19140, 77007, 77289, 77491, etc.).

  The dyes and pigments may be in individual form or in the form of a mixture and coated with each other, with different color effects generally resulting from different coating thicknesses. The total amount of dye and coloring pigment is, for example, in each case from 0.1% to 30% by weight, preferably from 0.5 to 15% by weight, in particular from 1.0 to 10% by weight, based on the total weight of the composition Is advantageously selected from the range of

  All compounds or components that can be used in the composition are known and commercially available or can be synthesized by known methods.

  One or more compounds of formula I can be incorporated into cosmetic or dermatological compositions in a conventional manner. Suitable compositions are for external use as a cream, lotion, gel form or as a solution that can be sprayed onto the skin. Suitable for internal use are administration forms such as capsules, coated tablets, powders, tablet-type solutions or solutions.

  Examples of application forms of the composition according to the invention that may be mentioned are: solutions, suspensions, emulsions, PIT emulsions, pastes, ointments, gels, creams, lotions, powders, soaps, detergent-containing cleaning preparations, Oils, aerosols and sprays.

  Examples of other application forms are sticks, shampoos and shower compositions. Any desired conventional excipients, adjuvants, and other active ingredients as desired can be added to the composition.

  Preferred adjuvants are those derived from the group of preservatives, antioxidants, stabilizers, solubilizers, vitamins, colorants, aroma improvers.

  Ointments, pastes, creams and gels are conventional excipients such as animal and vegetable oils, waxes, paraffin, starch, tragacanth, cellulose derivatives, polyethylene glycol, silicone, bentonite, silica, talc and zinc oxide, or Mixtures of these materials can be included.

  Powders and sprays can contain conventional excipients such as lactose, talc, silica, aluminum hydroxide, calcium silicate and polyamide powder, or mixtures of these substances. The propellant can further comprise conventional propellants such as chlorofluorocarbons, propane / butane or dimethyl ether.

  Solutions and emulsions are conventional excipients such as solvents, solubilizers and emulsifiers such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butyl glycol, Oils, particularly cottonseed oil, peanut oil, wheat germ oil, olive oil, castor oil and sesame oil, glycerol fatty acid esters, polyethylene glycols and fatty acid esters of sorbitan or mixtures of these substances may be included.

  Suspensions are conventional excipients such as liquid diluents such as water, ethanol or propylene glycol, suspensions such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol esters and polyoxyethylene sorbitan esters, microcrystalline Cellulose, aluminum metahydroxide, bentonite, agar as well as tragacanth, or a mixture of these materials can be included.

  Soaps are usually shaped like alkali metal salts of fatty acids, salts of fatty acid monoesters, fatty acid protein hydrolysates, isothionates, lanolins, fatty alcohols, vegetable oils, plant extracts, glycerol, sugars or mixtures of these substances An agent can be included.

  Surfactant-containing cleaning products are usually excipients such as salts of aliphatic alcohol sulfates, fatty alcohol ether sulfates, sulfosuccinic acid monoesters, fatty acid protein hydrolysates, isothionates, imidazolinium derivatives, methyl tau May include rate, sarcosinate, fatty acid amide ether sulfate, alkylamide betaine, fatty alcohol, fatty acid glyceride, fatty acid diethanolamide, vegetable and synthetic oils, lanolin derivatives, ethoxylated glycerol fatty acid esters, or mixtures of these substances .

  Face oils and body oils are ordinary excipients such as synthetic oils such as fatty acid esters, fatty alcohols and silicone oils, vegetable oils and oily plant extracts, natural oils such as paraffin oil and lanolin oil, or these substances. Can be included.

  Other common cosmetic application forms include lipstick, lip care stick, mascara, eyeliner, eye shadow, rouge, powder make-up, emulsion make-up and wax make-up and sunscreen, pre- and post-sun preparations .

  The preferred composition form according to the invention is in particular an emulsion.

  Emulsions are advantageous according to the invention, including, for example, the oils, oils, waxes and other oily substances, as well as water and emulsifiers commonly used in such compositions.

The lipid phase can be advantageously selected from the following group of substances:
-Mineral oil, mineral wax;
-Oils such as capric acid or caprylic acid triglycerides, as well as natural oils such as castor oil;
-Fats, waxes and other natural and synthetic fat substances, preferably esters of fatty acids with low-carbon alcohols such as isopropanol, propylene glycol or glycerol, or fatty alcohols and low-carbon alkanoic acids, Or esters of fatty acids;
-Silicone oils such as dimethylpolysiloxane, diethylpolysiloxane, diphenylpolysiloxane and mixtures thereof.

  For the purposes of the present invention, the oil phase of emulsions, oleogels or hydrodispersions or lipodispersions is saturated and / or unsaturated, branched and / or unbranched alkane carboxylic acids having a chain length of 3 to 30 C atoms. Acids and groups of saturated and / or unsaturated, branched and / or unbranched alcohol esters having a chain length of 3 to 30 C atoms, or chains of aromatic carboxylic acids and 3 to 30 C atoms It is advantageously selected from the group of saturated and / or unsaturated, branched and / or unbranched alcohol esters having a length. This kind of ester oil is isopropyl myristate, isopropyl palmitate, isopropyl stearate, isopropyl oleate, n-butyl stearate, n-hexyl laurate, n-decyl oleate, isooctyl stearate, isononyl stearate, isononane Of isononyl acid, 2-ethylhexyl palmitate, 2-ethylhexyl laurate, 2-hexyldecyl stearate, 2-octyldodecyl palmitate, oleyl oleate, oleyl erucate, erucyl oleate, and erucyl erucate It can advantageously be selected from the group of synthetic, semi-synthetic and natural mixtures, for example jojoba oil.

  The oil phase further comprises branched and unbranched hydrocarbons, as well as waxes, silicone oils, dialkyl ethers, saturated or unsaturated, branched or unbranched alcohols and fatty acid triglycerides, in particular 8-24, in particular 12-18. It can advantageously be selected from the group of saturated and / or unsaturated, branched and / or unbranched alkanecarboxylic acid triglycerol esters having a chain length of C atoms. The fatty acid triglycerides are advantageously selected from the group of, for example, synthetic, semi-synthetic and natural oils such as olive oil, sunflower oil, soybean oil, peanut oil, rapeseed oil, almond oil, coconut oil, coconut oil, palm kernel oil and the like. it can.

  Any desired mixture of such oil and wax components can also be used advantageously for the present invention. Waxes such as cetyl palmitate can also be used advantageously as the only lipid component of the oil phase.

The oil phase is 2-ethylhexyl isostearate, octyldodecanol, isotridecyl isononanoate, isoeicosane, 2-ethylhexyl cocoate, C ₁₂ ~ ₁₅ - alkyl benzoate, from the group of caprylic / capric acid triglyceride and dicaprylyl ether advantageously You can choose.

Particularly advantageous are, C ₁₂ ~ ₁₅ - alkyl benzoate, - mixtures of alkyl benzoate and 2-ethylhexyl isostearate, C ₁₂ ~ ₁₅ - mixtures of alkyl benzoate and isotridecyl isononanoate, as well as C ₁₂ ~ ₁₅ A mixture of 2-ethylhexyl isostearate and isotridecyl isononanoate.

  As hydrocarbons, paraffin oil, squalane and squalene can be advantageously used for the present invention.

  In addition, it is preferred that the oil phase contains a certain amount of cyclic or linear silicone oil, or consists entirely of this type of oil, but in addition to one or more silicone oils, other oil phase components are added. It is preferable to contain and use.

  The silicone oil used in the present invention is advantageously cyclomethicone (octamethylcyclotetrasiloxane). However, it is also advantageous for the present invention to use other silicone oils such as hexamethylcyclotrisiloxane, polydimethylsiloxane or poly (methylphenylsiloxane).

  Also particularly advantageous are mixtures of cyclomethicone and isotridecyl isononanoate, of cyclomethicone and 2-ethylhexyl isostearate.

  The aqueous phase of the composition according to the invention is optional, advantageously an alcohol, diol or polyol having a low carbon number, and its ether, preferably ethanol, isopropanol, propylene glycol, glycerol, ethylene glycol, ethylene glycol monoethyl. Or monobutyl ether, propylene glycol monomethyl, monoethyl or monobutyl ether, diethylene glycol monomethyl or monoethyl ether and the like, as well as alcohols having a low carbon number such as ethanol, isopropanol, 1,2-propanediol, glycerol, and 1 Containing one or more thickeners, especially silicon dioxide, aluminum silicate, polysaccharides and derivatives thereof, such as hyaluronic acid, xanthan Tangam, hydroxypropyl methylcellulose, particularly advantageously polyacrylates, preferably from the so-called Carbopol, for example from Carbopol grades 980, 981, 1382, 2984 or 5984, in each case individually or in combination from a group of polyacrylates You can choose.

  In particular, a mixture of the above solvents is used. In the case of alcoholic solvents, water can be a further component.

  Emulsions according to the invention advantageously comprise said oils, oils, waxes and other oily substances, as well as water and emulsifiers commonly used in such formulations.

  In a preferred embodiment, the composition according to the invention comprises a hydrophilic surfactant.

  The hydrophilic surfactant is preferably selected from the group of alkyl glucosides, acyl lactates, betaines and coconut amphoacetates.

  Alkyl glucoside itself has a structure

Wherein R represents a branched or unbranched alkyl group having 4 to 24 carbon atoms,

Represents an average degree of glucosylation of up to 2).

  value

Represents the degree of glucosylation of the alkyl glucoside used in the present invention,

_{(Wherein, p 1, p 2, p} 3 ... p i mono -, di -, tri -, ... i-fold represents a proportion by weight% of the glucosylated product) to be defined. It is advantageous to the present invention to select a product having a degree of glucosylation of 1-2, particularly preferably 1.1-1.5, very preferably 1.2-1.4, in particular 1.3. It is.

  The value DP takes into account the fact that as a result of its preparation, the alkyl glucoside is generally in the form of a mixture of mono- and oligoglucosides. A relatively high monoglucoside content, generally on the order of 40 to 70% by weight, is advantageous for the present invention.

  Particularly advantageous alkyl glycosides for use in the present invention are selected from the group of octyl glucopyranoside, nonyl glucopyranoside, decyl glucopyranoside, undecyl glucopyranoside, dodecyl glucopyranoside, tetradecyl glucopyranoside and hexadecyl glucopyranoside.

  Use natural or synthetic raw materials and adjuvants or mixtures identified by an effective content of the active ingredient used in the present invention, such as Plantaren® 1200 (Henkel KGaA), Oramix® NS 10 (Seppic) It is equally advantageous to do so.

  Acyl lactate itself has a structure

(Where
R ¹ represents a branched or unbranched alkyl group having ¹ to 30 carbon atoms,
M + is selected from the group of alkali metal ions and the group of ammonium ions substituted with one or more alkyl groups and / or one or more hydroxyalkyl groups, or 1/2 of the alkaline earth metal ions Are advantageously selected from the group of substances represented by

  For example, sodium isostearyl lactylate, such as the product Pathionic® ISL from the American Ingredients Company, is advantageous.

  Betaine is advantageously selected from the group of substances represented by the structure:

(Where
R ² represents a branched or unbranched alkyl group having 1 to 30 carbon atoms)
R ² particularly preferably represents a branched or unbranched alkyl group having 6 to 12 carbon atoms.

  For example, capramidopropyl betaine, such as Th. Goldschmidt AG's product Tego® etaine 810 is advantageous.

  A coconut amphoacetate which is advantageous according to the invention is, for example, sodium coconut amphoacetate which is commercially available under the name Miranol® Ultra C32 from Miranol Chemical Corp.

  In the composition according to the invention, the hydrophilic surfactant is in each case 0.01 to 20% by weight, preferably 0.05 to 10% by weight, particularly preferably 0.1%, based on the total weight of the composition. Advantageously, it is present at a concentration of ˜5% by weight.

  For use, the cosmetic and dermatological compositions according to the invention are applied to the skin and / or hair in a conventional manner and in an amount sufficient for cosmetics.

  The cosmetic and dermatological compositions according to the invention may exist in various forms. Thus, these include, for example, solutions, water-free compositions, water-in-oil (W / O) or oil-in-water (O / W) type emulsions or microemulsions such as water-in-oil-in-water (W / O / It may be in the form of W) type multiple emulsions, gels, solid sticks, ointments or aerosols. It is also advantageous to administer ectoine in encapsulated form, for example in collagen matrices and other conventional encapsulating materials, for example as cellulose capsules, in gelatin, wax matrix or in liposome-encapsulated form. In particular, it has been found that a wax matrix is preferred as described in DE-A 4308282. Emulsions are preferred. An O / W emulsion is particularly preferred. Emulsions, W / O emulsions and O / W emulsions can be obtained by conventional methods.

  Emulsifiers that can be used are, for example, the known W / O and O / W emulsifiers. In the preferred O / W emulsions according to the invention it is advantageous to use other usual co-emulsifiers.

  Co-emulsifiers which are advantageous in the invention are basically substances having an HLB value of, for example, 11-16, particularly preferably 14.5 as long as the O / W emulsifier has saturated groups R and R ′. O / W type emulsifiers from the group of substances having an HLB value of ˜15.5. If the O / W type emulsifier has an unsaturated group R and / or R 'or is an isoalkyl derivative, the preferred HLB value of such an emulsifier may be lower or higher.

  The fatty alcohol ethoxylate is advantageously selected from ethoxylated stearyl alcohol, cetyl alcohol, cetyl stearyl alcohol (cetearyl alcohol). Particularly preferred are: polyethylene glycol (13) stearyl ether (steareth-13), polyethylene glycol (14) stearyl ether (steareth-14), polyethylene glycol (15) stearyl ether (steareth-15), polyethylene Glycol (16) stearyl ether (steareth-16), polyethylene glycol (17) stearyl ether (steareless-17), polyethylene glycol (18) stearyl ether (steareth-18), polyethylene glycol (19) stearyl ether (steareth-19) , Polyethylene glycol (20) stearyl ether (steareless-20), polyethylene glycol (12) isostearyl ether (isosteareless-1) ), Polyethylene glycol (13) isostearyl ether (isosteares-13), polyethylene glycol (14) isostearyl ether (isosteares-14), polyethylene glycol (15) isostearyl ether (isosteares-15), polyethylene glycol (16) iso Stearyl ether (isosteares-16), polyethylene glycol (17) isostearyl ether (isosteares-17), polyethylene glycol (18) isostearyl ether (isosteares-18), polyethylene glycol (19) isostearyl ether (isosteares-19), Polyethylene glycol (20) isostearyl ether (isosteares-20), polyethylene glycol (13) cetyl Ether (ceteth-13), polyethylene glycol (14) cetyl ether (ceteth-14), polyethylene glycol (15) cetyl ether (ceteth-15), polyethylene glycol (16) cetyl ether (ceteth-16), polyethylene glycol (17 ) Cetyl ether (ceteth-17), polyethylene glycol (18) cetyl ether (ceteth-18), polyethylene glycol (19) cetyl ether (ceteth-19), polyethylene glycol (20) cetyl ether (ceteth-20), polyethylene glycol (13) Isocetyl ether (Isocetes 13), polyethylene glycol (14) Isocetyl ether (Isocetes-14), polyethylene glycol (15) Isocetyl ether (Isocetes-15), Polyethylene glycol (16) isocetyl ether (isocetes-16), polyethylene glycol (17) isocetyl ether (isocetes-17), polyethylene glycol (18) isocetyl ether (isocetes-18), polyethylene glycol (19) isocetyl ether (Isocetes-19), polyethylene glycol (20) isocetyl ether (isocetes-20), polyethylene glycol (12) oleyl ether (oles-12), polyethylene glycol (13) oleyl ether (oles-13), polyethylene glycol (14 ) Oleyl ether (Oles-14), Polyethylene glycol (15) Oleyl ether (Oles-15), Polyethylene glycol (12) Lauryl ether (Laureth-1) ), Polyethylene glycol (12) isolauryl ether (isolaureth-12), polyethylene glycol (13) cetyl stearyl ether (ceteales-13), polyethylene glycol (14) cetyl stearyl ether (ceteales-14), polyethylene glycol (15) cetyl Stearyl ether (ceteales-15), polyethylene glycol (16) cetyl stearyl ether (ceteares-16), polyethylene glycol (17) cetyl stearyl ether (ceteares-17), polyethylene glycol (18) cetyl stearyl ether (ceteares-18), Polyethylene glycol (19) cetyl stearyl ether (ceteales-19), polyethylene glycol (20) cetyl stearyl ether Ceteareth-20).

It is further advantageous to select from the following group of fatty acid ethoxylates:
Polyethylene glycol (20) stearate, polyethylene glycol (21) stearate, polyethylene glycol (22) stearate, polyethylene glycol (23) stearate, polyethylene glycol (24) stearate, polyethylene glycol (25) stearate, polyethylene glycol (12) Isostearate, polyethylene glycol (13) isostearate, polyethylene glycol (14) isostearate, polyethylene glycol (15) isostearate, polyethylene glycol (16) isostearate, polyethylene glycol (17) isostearate Rate, polyethylene glycol (18) isostearate, polyethylene glycol (19) isostearate, polyethylene glycol (20) Isostearate, Polyethylene glycol (21) Isostearate, Polyethylene glycol (22) Isostearate, Polyethylene glycol (23) Isostearate, Polyethylene glycol (24) Isostearate, Polyethylene glycol (25) Iso Stearate, polyethylene glycol (12) oleate, polyethylene glycol (13) oleate, polyethylene glycol (14) oleate, polyethylene glycol (15) oleate, polyethylene glycol (16) oleate, polyethylene glycol (17) oleate, polyethylene glycol (18) Oleate, polyethylene glycol (19) oleate, polyethylene glycol (20) oleate.

  The ethoxylated alkyl ether carboxylic acid or salt thereof which can be used is preferably sodium laureth-11 carboxylate. An alkyl ether sulfate which can advantageously be used is sodium laureth-14 sulfate. An ethoxylated cholesterol derivative which can advantageously be used is polyethylene glycol (30) cholesteryl ether. Polyethylene glycol (25) soyasterol has also been found to work. An ethoxylated triglyceride which can advantageously be used is polyethylene glycol (60) evening primrose glyceride.

  Further, polyethylene glycol (20) glyceryl laurate, polyethylene glycol (21) glyceryl laurate, polyethylene glycol (22) glyceryl laurate, polyethylene glycol (23) glyceryl laurate, polyethylene glycol (6) glyceryl caprate / caprate, polyethylene It is advantageous to select glycol (20) glyceryl oleate, polyethylene glycol (20) glyceryl isostearate, polyethylene glycol (18) glyceryl oleate (polyethylene glycol glycerol fatty acid esters from the group of cocoates).

  Polyethylene glycol (20) sorbitan monolaurate, polyethylene glycol (20) sorbitan monostearate, polyethylene glycol (20) sorbitan monoisostearate, polyethylene glycol (20) sorbitan monopalmitate, polyethylene glycol (20) sorbitan monooleate It is also advantageous to select sorbitan esters from the group of

Among the optional W / O emulsifiers, those that are advantageous for use in the present invention are:
Fatty alcohols with 8 to 30 C atoms, monoglycerols of saturated and / or unsaturated, branched and / or unbranched alkanecarboxylic acids with a chain length of 8 to 24, in particular 12 to 18 C atoms Esters, diglycerol esters of saturated and / or unsaturated, branched and / or unbranched alkanecarboxylic acids with a chain length of 8 to 24, in particular 12 to 18, C atoms, 8 to 24, in particular 12 to Saturated and / or unsaturated, monoglycerol ethers of branched and / or unbranched alcohols with a chain length of 18 C atoms, saturated and with a chain length of 8 to 24, in particular 12 to 18 C atoms Diglycerol ethers of / and unsaturated, branched and / or unbranched alcohols, having a chain length of 8 to 24, in particular 12 to 18 C atoms. And / or unsaturated, branched and / or unbranched propylene glycol esters of alkanecarboxylic acids and saturated and / or unsaturated branches having a chain length of 8 to 24, in particular 12 to 18 C atoms And / or sorbitan esters of unbranched alkanecarboxylic acids.

  Particularly advantageous W / O emulsifiers are glyceryl monostearate, glyceryl monoisostearate, glyceryl monomyristate, glyceryl monooleate, diglyceryl monostearate, diglyceryl monoisostearate, propylene glycol monostearate, propylene Glycol monoisostearate, propylene glycol monocaprylate, propylene glycol monolaurate, sorbitan monoisostearate, sorbitan monolaurate, sorbitan monocaprylate, sorbitan monoisooleate, sucrose distearate, cetyl alcohol, stearyl alcohol , Arachidyl alcohol, behenyl alcohol, isobehenyl alcohol, ceralkyl alcohol, chimyl alcohol, polyethylene glycol 2) stearyl ether (steareth-2), glyceryl monolaurate, glyceryl monocaprinate, glyceryl monocaprylate.

  Preferred compositions according to the present invention are particularly suitable for protecting human skin against aging processes and damage caused by oxidative stress, i.e. free radicals caused by sunlight exposure, heat or other effects. Yes. In this regard, there are a variety of dosage forms commonly used for application. For example, in the form of a lotion or emulsion such as cream or emulsion (O / W type, W / O type, O / W / O type, W / O / W type), oily-alcoholic , Oily-aqueous or hydroalcoholic gels or solutions, solid sticks, and may be prepared as an aerosol.

  The composition comprises cosmetic adjuvants commonly used in this type of composition, such as thickeners, softeners, moisturizers, surfactants, emulsifiers, preservatives, antifoams, fragrances, waxes, lanolins, Propellants, dyes and / or pigments that color the composition itself or the skin, and other ingredients commonly used in cosmetics can be included.

  The dispersant or solubilizer used may be an oil, wax or other oleaginous material, a lower monoalcohol or lower polyol or mixtures thereof. Particularly preferred monoalcohols or polyols include ethanol, isopropanol, propylene glycol, glycerol and sorbitol.

  Preferred embodiments of the present invention, apart from compounds of formula I or formula II, in the presence of water, for example fatty alcohols, fatty acids, fatty acid esters, in particular triglycerides of fatty acids, lanolin, natural and synthetic oils or waxes and An emulsion in the form of a protective cream or emulsion containing an emulsifier.

  Other preferred embodiments are oily lotions based on natural or synthetic oils and waxes, lanolin, fatty acid esters, especially triglycerides of fatty acids, or lower alcohols such as ethanol, or glycerol and / or glycerol such as propylene glycol And oily-alcoholic lotions based on fatty acids such as oils, waxes and triglycerides of fatty acids.

  The composition according to the invention may be in a form comprising one or more lower alcohol or polyol alcohol gels such as ethanol, propylene glycol or glycerol, and a thickener such as siliceous earth. Oily-alcoholic gels may contain natural or synthetic oils or waxes.

  Solid sticks consist of natural or synthetic waxes and oils, fatty alcohols, fatty acids, fatty acid esters, lanolin and other oily substances.

  When preparing the composition as an aerosol, conventional propellants such as alkanes, fluoroalkanes and chlorofluoroalkanes are generally used.

  The cosmetic composition can also be used to protect the hair against photochemical damage in order to prevent color changes, bleaching or mechanical property damage. In this case, suitable preparations are in the form of a wash-out shampoo, lotion, gel or emulsion, and the composition can be applied before or after shampooing, before or after coloring or bleaching, or before or after permanent wave. Apply. Lotions or gels for styling and treating hair, lotions or gels for brushing or blow waving, hair lacquers, permanent wave compositions, compositions for coloring or bleaching hair It is also possible to select. In addition to the compounds of formula I or formula II, the compositions having photoprotective properties include auxiliary agents used in such compositions, such as surface active agents, thickeners, polymers, softeners, preservatives. Can contain foam stabilizers, electrolytes, organic solvents, silicone derivatives, oils, waxes, anti-grease agents, dyes and / or pigments that color the composition itself or hair, or other ingredients commonly used in hair care .

  The invention further provides the preparation of a composition characterized in that at least one of the compounds of the formula I or II having the above-mentioned groups is mixed with excipients suitable as cosmetics, dermatologically or as food. It relates to a method and to the use of a compound of formula I or formula II for preparing a composition.

  The composition according to the present invention can be prepared using techniques well known to those skilled in the art.

  Mixing results in dissolution, emulsification or dispersion of the compound of Formula I or Formula II in the excipient.

  It was also confirmed that the compounds of formula I or formula II can have a stabilizing effect on the composition. Therefore, when used in the corresponding product, the latter (composition) also remains stable for a long time and its appearance does not change. Specifically, the effectiveness of ingredients, such as vitamins, is retained even when applied for long periods of time or stored for long periods of time. This is particularly advantageous in the case of compositions for protecting the skin against the effects of UV light, since these cosmetic products are exposed to particularly strong stresses by UV irradiation.

  The positive effect of the compounds of formula I or formula II makes them particularly suitable for use in cosmetic or pharmaceutical compositions.

  The properties of the compounds of formula I or formula II should likewise be considered favorable for use as foods, food supplements or functional foods. Further explanations for food are equally applicable to food supplements and functional foods.

  Foods that can be enriched with one or more compounds of formula I or formula II according to the invention include all ingredients suitable for consumption by animals or humans, for example vitamins and their provitamins , Oils, fats, minerals or amino acids are included (food may be solid or liquid, ie in the form of a drink)

  Accordingly, the present invention further relates to the use of a compound of formula I or formula II as a food additive for human or animal nutrition, which is a food or food supplement and comprises a corresponding excipient About.

  A food product that can be enriched with one or more compounds of formula I or formula II according to the invention is, for example, also a single naturally derived food, such as sugar, sweetened of a single plant species. Unsweetened juice, squash or puree, for example unsweetened apple juice (eg also a mixture of different types of apple juice), grapefruit juice, orange juice, boiled apple, apricot squash, tomato juice, tomato sauce, tomato puree Etc. Other examples of foods that can be enhanced with one or more compounds of the formula I or formula II according to the invention are corn or cereals from a single plant species and materials obtained from plant species of this type For example, cereal syrup, rye flour, flour or oat bran. Mixtures of this type of food are also suitable for enhancing the quality with one or more compounds of the formula I or formula II according to the invention. For example, multivitamin preparations, mineral mixtures or sweetened juices. Another example of a food product that can be enhanced with one or more compounds of Formula I or Formula II according to the present invention is for food compositions such as prepared cereals, biscuits, mixed beverages, yogurt and other children. Mention may be made of specially prepared foods, diet foods, low calorie foods or animal feeds.

  Accordingly, foods that can be enriched with one or more compounds of formula I or formula II according to the invention include carbohydrates, lipids, proteins, inorganic elements, trace elements, vitamins, water or active metabolism of plants and animals. All combinations suitable for edible product are included.

  Foods that can be enriched with one or more compounds of formula I or formula II according to the invention are administered orally, for example in the form of meals, pills, tablets, capsules, powders, syrups, solutions or suspensions. It is preferable to do.

  A food product according to the present invention enriched with one or more compounds of formula I or formula II can be prepared using techniques well known to those skilled in the art.

  Due to their action, the compounds of formula I or formula II are also suitable as pharmaceutical ingredients, and the compounds of formula I or formula II treat, for example, prophylactic treatment of skin inflammation and allergies, in certain cases Can be used to prevent cancer. The compounds of formula I or formula II are particularly suitable for the preparation of a medicament for the treatment of skin inflammation, allergies and hypersensitivity. In addition, vein tonic, cuperose inhibitors, chemical, physical or photo erythema inhibitors, sensitive skin treatments, decongestants, desiccants, skin wrinkles, wrinkle removers It is possible to prepare pharmaceuticals that act as agents, stimulants for synthesis of extracellular matrix components, enhancers for improving skin elasticity, and anti-aging agents. Furthermore, preferred compounds of formula I or formula II in this connection exhibit antiallergic, antiinflammatory and antihypersensitive effects. They are therefore suitable for the preparation of medicaments for the treatment of inflammation or allergic reactions.

  Preferred anti-inflammatory compositions can comprise at least one additional anti-inflammatory active ingredient. It is preferably selected from glucocorticoids or tacrolimus.

  Tacrolimus is isolated from the fungus Streptomyces tsukakaensis and exhibits immunosuppressive action.

  Suitable glucocorticoids include, for example, prednisone, clopredanol, triamcinolone, methylprednisolone, dexamethasone, betamethasone, dezoxymethazone, clobetasone butyrate, halcinonide, clobetasol pyropionate, prednisolone, hydrocortisone butyrate flusizoneon didipiropionate, Ocinolone acetonide, betamethasone valerate, hydrocortisone (cortisol), cortisone acetate, prednisocarbate diflucortron valerate, triamcinolone acetonide, fluocinolone acetonide, fluocortron and fluocortron 21-hexanoate.

  This type of composition comprising an active ingredient combination of at least one complex compound of formula I or at least one compound of formula II and at least one cyclodextrin and at least one of the above-mentioned anti-inflammatory active ingredients is in particular Strong inhibitory effect on inflammation.

  In particular, it has been found that the complex compounds and compositions of formula I according to the invention can be used particularly advantageously for the treatment of atopic eczema, in particular chyle, neurodermatitis, prurigo and proliferative dermatitis. It was.

These are
-Can significantly reduce acute symptoms;
-The frequency of acute symptoms can be reduced,
− It has been found that it generally contributes to the improvement of the skin condition.

  Compositions comprising one or more compounds of formula I are also suitable for protecting human skin against oxidative stress, ie free radical damage caused by, for example, sunlight, heat or other effects, or somatic cells. Yes.

  Compositions comprising one or more compounds of formula I are particularly suitable for inhibiting skin aging.

  The invention therefore also relates to the use of one or more compounds of the formula I as active ingredients for protection against oxidative stress. The invention further relates to the use of one or more compounds of formula I for preventing skin aging.

  The compounds of formula I have anti-allergic, anti-inflammatory, anti-inflammatory and anti-hypersensitivity properties and are therefore especially for the treatment or prophylactic treatment of skin allergies, inflammation and hypersensitivity Can be used. The invention therefore further relates to the use of one or more compounds of the formula I as active ingredients having antiallergic, anti-inflammatory, anti-inflammatory and anti-hypersensitive effects.

  A preferred use in the present invention of a compound of formula I or a composition comprising at least one of the compounds of formula I prevents the time and / or light-induced aging process of human skin or human hair, in particular dry skin, wrinkles And / or prevent pigment abnormalities and / or reduce or prevent the damaging effects of UV light on the skin, and skin unevenness such as wrinkles, fine lines, rough skin or large pore skin Use to prevent skin or reduce skin non-uniformity.

When the compounds used in the present invention have a free hydroxyl group, in addition to the properties described above, they further exhibit an action as an antioxidant and / or free radical scavenger. Accordingly, it has photoprotective properties comprising at least one compound of formula I, characterized in that at least one of the radicals R ^{1 to} R ³ represents OH, preferably at least one of the radicals R ¹ and R ² represents OH Compositions are also preferred.

  It is preferred to allow the compound of formula I to penetrate more deeply into the skin layer, since the compound of formula I can bring particularly positive action as a free radical scavenger on the skin. There are several possibilities for this. First, the compound of formula I can have sufficient lipophilicity so that it can penetrate through the outer skin layer into the epidermis layer. As another possibility, corresponding transport agents capable of transporting the compound of formula I through the outer skin layer, for example liposomes, can also be provided in the composition. Finally, systemic transport of compounds of formula I is also conceivable. That is, the composition is designed, for example, in a form suitable for oral administration.

  In general, the substances of formula I act as free radical scavengers. This type of free radical is generated not only by light but under various conditions. Examples of hypoxia that block the flow of electrons upstream of cytochrome oxidase and cause the production of superoxide free radical anions are related, inter alia, to the production of superoxide anions by leukocyte membrane NADPH oxidants and are usually phagocytic Inflammation associated with the formation of hydroxyl radicals and other reactive species with phenomena (by disproportionation in the presence of iron (II) ions), and lipid-based alkoxy radicals generally initiated by hydroxyl radicals And autoxidation of lipids to produce hydroperoxides.

  Preferred compounds of formula I are believed to also act as enzyme inhibitors. These are presumed to inhibit histidine decarboxylase, protein kinase, elastase, aldose reductase and hyaluronidase, thus allowing the basic substance of the vascular sheath to be kept intact. Furthermore, they are presumed to result in non-specific inhibition of catechol O-methyltransferase, thereby increasing the amount of available catecholamine and thus increasing vascular strength. Furthermore, they inhibit AMP phosphodiesterase, resulting in the possibility that this substance inhibits platelet aggregation.

  Because of these properties, the compositions according to the invention are generally suitable for immune protection and DNA and RNA protection. In particular, the composition is suitable for protecting DNA and RNA against damage due to oxidative attack, free radicals and irradiation, in particular UV irradiation. Another advantage of the composition according to the invention is cell protection, in particular the protection of Langerhans cells against damage due to the above effects. All these uses, and the use of compounds of formula I for the preparation of correspondingly usable compositions, are also clearly the subject of the present invention.

  Specifically, preferred compositions according to the present invention are particularly useful for the treatment of skin diseases associated with defects in keratinization that affect differentiation and cell proliferation, particularly acne vulgaris, comedonica, Acne vulgaris, acne rosaceae, nodular acne, conglobata, age-induced acne, acne that occurs as a side effect, for example, acne solaris, drug-induced acne For the treatment of acne or acne professionalis, other defects in keratinization, especially ichthyosis, ichthyosis-like conditions, Darier's disease, palmokeratosis, leukoplakia, leukoplakia-like condition, skin and For the treatment of mucous membrane (oral) (lichen) herpes, other skin diseases associated with defects in keratinization and having inflammatory and / or immunoallergenic components, in particular skin, mucous membranes and fingers and feet of hands All forms of psoriasis affecting the fingernails, psoriatic rheuma And skin atopy, such as eczema or respiratory atopy or gum (gum) are also suitable for the treatment of such hypertrophy. In addition, this compound has benign or malignant protrusions of all dermis or epidermis that may be virus-derived, such as common warts, flat warts, warts, due to some inflammation not associated with defects in keratinization Dermatitis for the treatment of epidermoid dysplasia, oral papillomatosis, papillomatosis Florida (florida), and protrusions that may be caused by UV irradiation, especially basal cell epithelioma and squamous cell epithelioma To combat and combat light-induced skin aging associated with aging for the treatment of other skin diseases such as bullous diseases and diseases affecting collagen, especially for the treatment of certain eye diseases, especially corneal diseases, Corticostery applied topically or systemically to reduce pigmentation and keratosis actinica, to treat all diseases associated with normal aging or light-induced aging Skin striae brought about by pregnancy to prevent or cure wounds / scarring of epidermis and / or dermis atrophy and all other types of skin atrophy caused by or for the prevention or treatment of defects in wound healing Cancerous or pre-cancerous conditions, especially myeloid, to prevent or eliminate or to combat wound healing defects such as excessive or simple seborrhea in acne To fight or prevent leukemia, to treat inflammatory diseases such as arthritis, to treat all virus-induced diseases of the skin or other parts of the body, to prevent or treat alopecia, skin Cardiovascular diseases such as arteriosclerosis or hypertension and non-insulin dependent for the treatment of diseases or diseases of other parts of the body with immunological components For the treatment of diabetes it can also be used for the treatment of skin defects caused by UV radiation.

  Furthermore, the inherent color of the compound of formula I is very light. The light native color is a major advantage when, for example, the product does not want the inherent color of the component for aesthetic reasons.

  The proportion of the compound of formula I in the composition is preferably from 0.01 to 20% by weight, particularly preferably from 0.05 to 10% by weight, particularly preferably from 0.1 to 5% by weight, based on the total composition It is. The proportion of the compound of formula I in the composition is very preferably from 0.1 to 2% by weight, based on the total composition.

Even in the absence of other comments, those skilled in the art should be able to use the above description to the broadest extent. Accordingly, the preferred embodiments are to be regarded as illustrative disclosures that are in no way limiting in any way. The entire disclosures of all applications and documents listed above and below are incorporated herein by reference. The following examples are intended to illustrate the present invention. However, these should not be considered limiting. All compounds or components that can be used in the composition are either known or commercially available or can be synthesized by known methods. The INCI names of the raw materials used are as follows:
Example List of raw materials used

Example A-Preparation of Tyriloside / Cyclodextrin Complex Initially 0.9 g of hydroxypropyl gamma-cyclodextrin (Aldrich; 2'-hydroxypropylcyclooctaamylose; Cas. No. 128446-34-4) in 8 ml of water. In addition, warm to 50 ° C. 0.15 g of tiliroside is dissolved in 8 ml of ethanol at room temperature and added dropwise to the initially added solution. The solution is stirred at 50 ° C. for 3 days. Ethanol is distilled off from the solution. The residue is dried under reduced pressure, and the resulting yellow solid is post-dried at 40 ° C. and 200 mbar overnight. Yield: 1.02 g = 97.2 theoretical% of yellow crystalline residue.

Characterization:
-Evidence for complex formation by 2D-NMR spectrum The ROESY spectrum shows the interaction of spatially close atoms. Spatially close atoms give a signal in the ROESY 2D-NMR spectrum. Here, the complex was measured by ROESY to reveal the molecular components of tiliroside through which complex formation occurs.

In the ROESY spectrum (solvent D ₂ O), a signal is generated that can be attributed to the interaction of the tiliroside atoms 2 ′ ″, 3 ′ ″, 6 and 8 (see structural diagram) with the cyclodextrin molecule.

  The NMR data fits the interpretation that a complex consisting of tyriloside and two cyclodextrin molecules spatially arranged on the aromatic ring of coumaric acid or ring B of the flavone substructure is formed.

-The content of tiliroside in the solids (determined by HPLC)
8.0 mg of tiliroside is dissolved in 3 ml of methanol and 1 ml of THF and made up to 10.0 ml with eluent (acrylonitrile / H ₂ O 2/8) in a volumetric flask (peak area of 12783970).

11.5 mg of the complex is dissolved in 3 ml methanol and 1 ml tetrahydrofuran and made up to 10.0 ml with eluent (acrylonitrile / H ₂ O 2/8) in a volumetric flask. (Tiriloside peak area 2503977).

Calculation: 8.0 mg of tiliroside has an area of 12783970 11.5 mg of tiliroside has an area of 18376957 An area of 2503997 is observed.

As a result: the complex consists of 13.6% by weight of tiliroside. In the complex, the weight ratio of tiliroside: cyclodextrin is 13.6: 86.4. This corresponds to a molar ratio of 1: 2 (tiriloside (cyclodextrin) ₂ complex = 14.4: 85.6 theoretical weight ratio).

  The complex compound is a [tyryloside] [hydroxypropyl γ-cyclodextrin] 2 complex.

Solubility of tiliroside / cyclodextrin complex:
0.5 g of the complex is dissolved in 1 ml of water without reaching saturation. This is on a pure tiriloside basis and corresponds to a solubility of at least 72 mg / ml.

  In the formulations 1 to 5 of the following examples, in each case tiliroside is used as the tiliroside / hydroxypropyl γ-cyclodextrin complex according to example A.

Example 1
Lotion for applying to the skin (W / O type)
weight%
A Polyglyceryl 2-dipolyhydroxystearate 5.0
Beeswax 0.5
Zinc stearate 0.5
Hexyl laurate 9.0
Cetyl isononanoate 6.0
Shea butter 0.5
DL-α-tocopherol acetate 1.0
Tiriloside 0.5
B Glycerol 5.0
Magnesium sulfate heptahydrate 1.0
Preservative Sufficient amount Demineralized water Sufficient amount up to 100.

Preparation Warm Phase A to 75 ° C and Phase B to 80 ° C. Add Phase B to Phase A with stirring. After homogenization, the mixture is cooled with stirring. Add fragrance at a temperature of 40 ° C. Use the following as preservatives:
0.05% propyl 4-hydroxybenzoic acid 0.15% methyl 4-hydroxybenzoic acid.

Example 2
Lotion for applying to the skin (W / O type)
weight%
A Polyglyceryl 2-dipolyhydroxystearate 5.0
Beeswax 0.5
Zinc stearate 0.5
Hexyl laurate 9.0
Cetyl isononanoate 6.0
Shea butter 0.5
DL-α-tocopherol acetate 1.0
B Sulfated tiliroside, sodium salt (Example A) 1.0
Glycerol 5.0
Magnesium sulfate heptahydrate 1.0
Preservative Sufficient amount Demineralized water Sufficient amount up to 100.

Preparation Warm Phase A to 75 ° C and Phase B to 80 ° C. Add Phase B to Phase A with stirring. After homogenization, the mixture is cooled with stirring. Add fragrance at a temperature of 40 ° C. Use the following as preservatives:
0.05% propyl 4-hydroxybenzoate 0.15% methyl 4-hydroxybenzoate.

Example 3
Lotion for applying to the skin (W / O type)
weight%
A 4,6,3 ′, 4′-Etrahydroxybenzylcoumaranone-3
1.0
Polyglyceryl 2-dipolyhydroxystearate 5.0
Beeswax 0.5
Zinc stearate 0.5
Hexyl laurate 9.0
Cetyl isononanoate 6.0
Shea butter 0.5
DL-α-tocopherol acetate 1.0
Tiriloside 1.0
B Glycerol 5.0
Magnesium sulfate heptahydrate 1.0
Preservative Sufficient amount Demineralized water Sufficient amount up to 100.

Preparation Warm Phase A to 75 ° C and Phase B to 80 ° C. Add Phase B to Phase A with stirring. After homogenization, the mixture is cooled with stirring. Add fragrance at a temperature of 40 ° C. Use the following as preservatives:
0.05% propyl 4-hydroxybenzoate 0.15% methyl 4-hydroxybenzoate.

Example 4
A cream containing ectoine (O / W type) is prepared from the following ingredients:
weight%
A Paraffin, liquid (1) 8.0
Isopropyl myristate (1) 4.0
Mirasil CM5 (2) 3.0
Stearic acid (1) 3.0
Arlacel 165V (3) 5.0
Tiriloside 1.0
B Glycerol (87%) (1) 3.0
Germaben II (4) 0.5
Deionized water Sufficient to 100 C RonaCare (TM) ectoine (1) 1.0.

Preparation First, phase A and phase B are separately heated to 75 ° C. Then phase A is slowly added to phase B with stirring and stirred until a uniform mixture is formed. After homogenizing the emulsion, the mixture is cooled to 30 ° C. with stirring. Subsequently, the mixture is warmed to 35 ° C., phase C is added, and the mixture is stirred until homogeneous. Source (1) Merck KGaA
(2) Rhodia
(3) Uniqema
(4) ISP.

Example 5
Topical composition as W / O emulsion
weight%
A Isolan PDI (2) 3.0
Paraffin oil, liquid (1) 17.0
Isopropyl myristate 5.0
Beeswax 0.2
Cutina HR (2) 0.3
Tiriloside 1.0
B Demineralized water Sufficient amount up to 100 Glycerol (87%) 4.0
Magnesium sulfate 1.0
Germaben II-E (3) 1.0
C RonaCare (TM) LPO (1) 2.0.

Preparation Warm Phase A and Phase B to 75 ° C. Add Phase B to Phase A with stirring. Subsequently, the mixture is homogenized with Turrax at 9000 rpm for 2 minutes. Cool the resulting mixture to 30-35 ° C. and mix in Phase C. Supplier (1) Merck KGaA
(2) Goldschmidt AG
(3) ISP.

Example 6: Composition The preparation of a cosmetic composition comprising a tiliroside / 2-hydroxypropyl γ-cyclodextrin complex (= tyriloside / CD) according to Example A is shown in the following example. Furthermore, the INCI name of a commercially available compound is shown.

  UV-Pearl, OMC represents a composition having the INCI name: water (for EU: Aqua), ethylhexyl methoxycinnamate, silica, PVP, Chlorphenesin, BHT; This composition is commercially available from Merck KGaA, Darmstadt under the name Eusolex® UVPearl ™ OMC.

  The other UV-Pearl shown in each table has a similar composition. However, the OMC has been replaced with the UV filter shown.

Claims (20)

Complex compounds of formula I

(Where
Z _{1 to} Z ₄ and Z _{6 to} Z ₁₀ each independently represent H, OH, CH ₃ COO, alkoxy, hydroxyalkoxy, mono- or oligoglycoside group, and the alkoxy and hydroxyalkoxy groups are branched or unbranched. Well, it can have 1 to 18 C atoms,

Is

Represents
Z ₅ is a mono- or oligoglycoside group, which in each case via an —O— group,

(Where
X, X ₁ , X ₂ and X ₃ each independently represent OH, CH ₃ COO, an alkoxy group having 1 to 8 C atoms or a monoglycoside group,
n is 0, 1, 2 or 3;
m is 0 or 1,
k is 0, 1, 2, 3 or 4;
M is H, Na or K)
And at least one group selected from
CD represents a cyclodextrin molecule,
o represents the number 1,
p represents a numerical value in the range of 0.5 to 3,
One or more hydrogen atoms are each acetyl or C ₁ ~ ₂₄ independently of each other OH groups of the glycoside radicals in the substituent Z ₁ to Z ₁₀ - it may be substituted with an alkyl group, sulfate or phosphate Each salt may be independently of one another bound to one or more hydroxyl groups of the above groups in the substituents Z _{1 to} Z ₁₀ ). The cyclodextrin CD is alpha-, beta-or γ- cyclodextrin, preferably one or more hydroxyl groups C ₁ ~ ₂₄ - alkyl - or C ₁ ~ ₂₄ - optionally substituted with hydroxyalkyl γ- 2. Complex compound according to claim 1, characterized in that it is a cyclodextrin, particularly preferably hydroxypropyl-γ-cyclodextrin. Wherein the flavonoid moiety is a compound of formula IIA

(Where
R ¹ , R ² and R ³ each independently represent OH, CH ₃ COO, an alkoxy group having 1 to 8 C atoms or a monoglycoside group,
R ⁴ is a mono- or diglycoside group, which in each case through an —O— group,

(Wherein R ⁵ , R ⁶ and R ⁷ are each independently H or have the meaning of the radicals R ^{1 to} R ³ )
And at least one group selected from
Wherein the one or more hydrogen atoms are independently of each other OH group of the glycoside radical, acetyl or C ₁ ~ ₂₄ - it may be substituted with an alkyl group, independently of each other sulfate or phosphate, formula IIA Which may be bonded to one or more hydroxyl groups of
The complex compound according to claim 1, wherein the complex compound is one or more compounds selected from the group consisting of: The compound of formula IIA is a compound of formula IIA1 and IIA2

The complex compound according to claim 3, wherein the complex compound is selected from the group consisting of:   The flavonoid moiety is used in the form of a plant extract or purified plant extract, or in the form of a high purity material prepared from a plant extract, wherein the plant extract is 5 to 90% by weight of a flavonoid of formula I The complex compound according to claim 1, wherein the complex compound is contained.   The complex compound according to at least one of the preceding claims, wherein o in the formula I is 1, p is in the range of 1.75 to 2.1, and p is preferably 2. Compound of formula II

(Where
Z _{1 to} Z ₄ and Z _{6 to} Z ₁₀ each independently represent H, OH, CH ₃ COO, alkoxy, hydroxyalkoxy, mono- or oligoglycoside group, and the alkoxy and hydroxyalkoxy groups are branched or unbranched. Well, it can have 1 to 18 C atoms,

Is

Represents
Z ₅ is a mono- or oligoglycoside group, which in each case via an —O— group,

(In the formula, X, X ₁ , X ₂ and X ₃ each independently represent OH, CH ₃ COO, an alkoxy group having 1 to 8 C atoms or a monoglycoside group, and n is 0, 1, 2 or 3, m is 0 or 1, k is 0, 1, 2, 3 or 4, and M is H, Na or K). cage, one or more hydrogen atoms are each acetyl or C ₁ ~ ₂₄ independently of each other OH groups of the glycoside radicals in the substituent Z ₁ to Z ₁₀ - it may be substituted with an alkyl group, sulfate or The phosphates may be bonded independently of one another to one or more hydroxyl groups of the above groups in the substituents Z _{1 to} Z ₁₀ )
The method of preparing a complex compound according to at least one of claims 1 to 6, characterized in that it is reacted with cyclodextrin CD in solution, preferably at elevated temperature.   8. Process according to claim 7, characterized in that the cyclodextrin is used in excess or exactly in a molar ratio of 2: 1 with respect to the flavonoids of the formula II. A composition comprising suitable excipients,
Containing 0.005 to 99% by weight of the complex compound of formula I according to claim 1, or wherein the composition comprises
0.002 to 70% by weight of cyclodextrin;
Composition comprising at least 0.001 to 60% by weight of at least one compound of formula II according to claim 7, or a locally tolerated salt and / or derivative thereof.   One or more compounds of the formula I are present in the composition in an amount of 0.01 to 20% by weight, preferably 0.05 to 10% by weight, particularly preferably 0.1 to 5% by weight. The composition according to claim 9.   The content of cyclodextrin in the composition is in each case 0.01 to 20.0% by weight, preferably 0.05 to 10.0% by weight, particularly preferably 0.1%, based on the total weight of the composition. To 5.0% by weight, and the content of the compound of formula II in the composition is 0.01 to 20% by weight, preferably 0.05 to 10% by weight, particularly preferably 0, based on the total composition. 1 to 5% by weight, and the proportion of the compound of formula II in the composition is very preferably in the range from 0.1 to 2% by weight relative to the total composition. 10. The composition according to 9.   The composition according to at least one of the preceding claims, wherein the composition comprises one or more antioxidants and / or one or more UV filters.   Said composition comprises one or more other active ingredients having skin care and / or inflammation inhibiting action, said one or more other active ingredients being preferably glucocorticoid or tacrolimus A composition according to at least one of the preceding claims.   14. Complex compound of formula I or at least one of claims 9 to 13 for the prevention and / or treatment of eczema, in particular atopic eczema, in particular chyle, neurodermatitis, urticaria and proliferative dermatitis. Use of the composition.   Use of a complex compound of formula I or a composition according to at least one of claims 9 to 13 for the care, protection or amelioration of the general condition of the skin or hair.   Prevent the time and / or light-induced aging process of human skin or human hair, in particular prevent dry skin, wrinkles and / or pigment abnormalities and / or reduce the damaging effects of UV light on the skin or Use of a complex compound of formula I or a composition according to at least one of claims 9 to 13 for prevention.   14. A complex compound of formula I for preventing or reducing skin heterogeneity, such as wrinkles, fine lines, rough skin or skin with large pores, or at least one of claims 9 to 13 Use of the described composition.   Use of a complex compound of formula I or a composition according to at least one of claims 9 to 13 for the prevention and / or treatment of inflammation or allergic reactions.   10. At least one compound of formula II and cyclodextrin or at least one compound of formula I having said group are mixed with excipients suitable as cosmetics or dermatologically or as food. 14. A method for preparing the composition according to at least one of items 13 to 13.   Use of a compound of formula I for the preparation of a composition according to at least one of claims 9 to 13.